Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas

Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissu...
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Autor*in:	Aslan, Katrin [verfasserIn] Turco, Verena [verfasserIn] Blobner, Jens - 1991- [verfasserIn] Sonner, Jana K. [verfasserIn] Liuzzi, Anna Rita [verfasserIn] Núñez, Nicolás Gonzalo [verfasserIn] De Feo, Donatella [verfasserIn] Vollmuth, Philipp - 1987- [verfasserIn] Fischer, Manuel [verfasserIn] Green, Ed [verfasserIn] Sadik, Ahmed [verfasserIn] Friedrich, Mirco [verfasserIn] Sanghvi, Khwab - 1990- [verfasserIn] Kilian, Michael - 1990- [verfasserIn] Cichon, Frederik - 1983- [verfasserIn] Wolf, Lara [verfasserIn] Jähne, Kristine [verfasserIn] von Landenberg, Anna [verfasserIn] Bunse, Lukas - 1988- [verfasserIn] Sahm, Felix - 1984- [verfasserIn] Schrimpf, Daniel - 1984- [verfasserIn] Meyer, Jochen [verfasserIn] Alexander, Allen [verfasserIn] Brugnara, Gianluca [verfasserIn] Röth, Ralph [verfasserIn] Pfleiderer, Kira [verfasserIn] Niesler, Beate [verfasserIn] Deimling, Andreas von - 1959- [verfasserIn] Opitz, Christiane - 1979- [verfasserIn] Breckwoldt, Michael O. - 1983- [verfasserIn] Heiland, Sabine [verfasserIn] Bendszus, Martin [verfasserIn] Wick, Wolfgang - 1970- [verfasserIn] Becher, Burkhard [verfasserIn] Platten, Michael - 1971- [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	18 February 2020

Anmerkung:	Gesehen am 22.10.2020
Umfang:	14

Übergeordnetes Werk:	Enthalten in: Nature Communications - [London] : Springer Nature, 2010, 11(2020) Artikel-Nummer 931, 14 Seiten
Übergeordnetes Werk:	volume:11 ; year:2020 ; extent:14

Links:	Volltext Volltext

DOI / URN:	10.1038/s41467-020-14642-0

Katalog-ID:	1736256467

Internformat


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245	1	0	\|a Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas \|c Katrin Aslan, Verena Turco, Jens Blobner, Jana K. Sonner, Anna Rita Liuzzi, Nicolás Gonzalo Núñez, Donatella De Feo, Philipp Kickingereder, Manuel Fischer, Ed Green, Ahmed Sadik, Mirco Friedrich, Khwab Sanghvi, Michael Kilian, Frederik Cichon, Lara Wolf, Kristine Jähne, Anna von Landenberg, Lukas Bunse, Felix Sahm, Daniel Schrimpf, Jochen Meyer, Allen Alexander, Gianluca Brugnara, Ralph Röth, Kira Pfleiderer, Beate Niesler, Andreas von Deimling, Christiane Opitz, Michael O. Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher & Michael Platten
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520			\|a Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB.
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982			\|2 2013 \|1 02 \|x DE-16-250 \|8 07 \|s s \|a pos_13

Indexfelder

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matchkey_str	article:20411723:2020----::eeoeetorsostimncekonbokdihprua
oclc_num	1341373260
hierarchy_sort_str	18 February 2020
publishDate	2020
allfields	10.1038/s41467-020-14642-0 doi (DE-627)1736256467 (DE-599)KXP1736256467 (OCoLC)1341373260 DE-627 ger DE-627 rda eng Aslan, Katrin verfasserin (DE-588)122006131X (DE-627)1736266896 aut Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas Katrin Aslan, Verena Turco, Jens Blobner, Jana K. Sonner, Anna Rita Liuzzi, Nicolás Gonzalo Núñez, Donatella De Feo, Philipp Kickingereder, Manuel Fischer, Ed Green, Ahmed Sadik, Mirco Friedrich, Khwab Sanghvi, Michael Kilian, Frederik Cichon, Lara Wolf, Kristine Jähne, Anna von Landenberg, Lukas Bunse, Felix Sahm, Daniel Schrimpf, Jochen Meyer, Allen Alexander, Gianluca Brugnara, Ralph Röth, Kira Pfleiderer, Beate Niesler, Andreas von Deimling, Christiane Opitz, Michael O. Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher & Michael Platten 18 February 2020 14 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 22.10.2020 Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. Turco, Verena verfasserin aut Blobner, Jens 1991- verfasserin (DE-588)1236368029 (DE-627)1761726706 aut Sonner, Jana K. verfasserin aut Liuzzi, Anna Rita verfasserin aut Núñez, Nicolás Gonzalo verfasserin aut De Feo, Donatella verfasserin aut Vollmuth, Philipp 1987- verfasserin (DE-588)1043270086 (DE-627)771319177 (DE-576)394600738 aut Fischer, Manuel verfasserin (DE-588)1155954491 (DE-627)1018513051 (DE-576)501959688 aut Green, Ed verfasserin aut Sadik, Ahmed verfasserin aut Friedrich, Mirco verfasserin aut Sanghvi, Khwab 1990- verfasserin (DE-588)1201828864 (DE-627)1685962580 aut Kilian, Michael 1990- verfasserin (DE-588)1220319422 (DE-627)1736693255 aut Cichon, Frederik 1983- verfasserin (DE-588)1220319589 (DE-627)1736693700 aut Wolf, Lara verfasserin aut Jähne, Kristine verfasserin aut von Landenberg, Anna verfasserin aut Bunse, Lukas 1988- verfasserin (DE-588)1051941229 (DE-627)787187399 (DE-576)407600426 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Schrimpf, Daniel 1984- verfasserin (DE-588)1063355044 (DE-627)812332032 (DE-576)422629529 aut Meyer, Jochen verfasserin (DE-588)1136398953 (DE-627)89281201X (DE-576)490511716 aut Alexander, Allen verfasserin aut Brugnara, Gianluca verfasserin (DE-588)1197163123 (DE-627)1678969850 aut Röth, Ralph verfasserin (DE-588)1068410221 (DE-627)820235563 (DE-576)427767059 aut Pfleiderer, Kira verfasserin (DE-588)1220060496 (DE-627)1736264265 aut Niesler, Beate verfasserin (DE-588)1066800693 (DE-627)817949615 (DE-576)426148452 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Opitz, Christiane 1979- verfasserin (DE-588)132405121 (DE-627)522675913 (DE-576)299125041 aut Breckwoldt, Michael O. 1983- verfasserin (DE-588)1022496298 (DE-627)716993392 (DE-576)365498297 aut Heiland, Sabine verfasserin (DE-588)106732626X (DE-627)818624450 (DE-576)426561368 aut Bendszus, Martin verfasserin (DE-588)1032676426 (DE-627)738634131 (DE-576)175567697 aut Wick, Wolfgang 1970- verfasserin (DE-588)120297736 (DE-627)080586929 (DE-576)186221320 aut Becher, Burkhard verfasserin aut Platten, Michael 1971- verfasserin (DE-588)121627780 (DE-627)081431848 (DE-576)261969811 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 11(2020) Artikel-Nummer 931, 14 Seiten Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:11 year:2020 extent:14 https://doi.org/10.1038/s41467-020-14642-0 Verlag Resolving-System lizenzpflichtig Volltext https://www.nature.com/articles/s41467-020-14642-0 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 14 11(2020) Artikel-Nummer 931, 14 Seiten 2013 01 DE-16-250 3784659160 00 --%%-- --%%-- --%%-- --%%-- l01 22-10-20 2013 02 DE-16-250 3789066648 00 --%%-- --%%-- --%%-- --%%-- l02 29-10-20 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_35 2013 01 DE-16-250 03 s s_14 2013 01 DE-16-250 04 p (DE-627)1761986880 Blobner, Jens 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_3 2013 01 DE-16-250 05 p (DE-627)1477787631 Vollmuth, Philipp 2013 01 DE-16-250 05 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1571959866 Fischer, Manuel 2013 01 DE-16-250 06 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1736694766 Kilian, Michael 2013 01 DE-16-250 07 k (DE-627)1416468684 Neurologische Klinik 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_14 2013 01 DE-16-250 08 p (DE-627)1736694928 Cichon, Frederik 2013 01 DE-16-250 08 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_15 2013 01 DE-16-250 09 p (DE-627)147761074X Bunse, Lukas 2013 01 DE-16-250 09 k (DE-627)1416468684 Neurologische Klinik 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 10 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_20 2013 01 DE-16-250 11 p (DE-627)1546527052 Schrimpf, Daniel 2013 01 DE-16-250 11 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_21 2013 01 DE-16-250 12 p (DE-627)1678969923 Brugnara, Gianluca 2013 01 DE-16-250 12 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_24 2013 01 DE-16-250 13 p (DE-627)1497767520 Röth, Ralph 2013 01 DE-16-250 13 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_25 2013 01 DE-16-250 14 p (DE-627)1736264397 Pfleiderer, Kira 2013 01 DE-16-250 14 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_26 2013 01 DE-16-250 15 p (DE-627)1497767695 Niesler, Beate 2013 01 DE-16-250 15 k (DE-627)1416741429 Institut für Humangenetik 2013 01 DE-16-250 15 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_27 2013 01 DE-16-250 16 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 16 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_28 2013 01 DE-16-250 17 p (DE-627)1502169614 Opitz, Christiane 2013 01 DE-16-250 17 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_29 2013 01 DE-16-250 18 p (DE-627)156023394X Breckwoldt, Michael O. 2013 01 DE-16-250 18 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 18 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 18 s pos_30 2013 01 DE-16-250 19 p (DE-627)1496564405 Heiland, Sabine 2013 01 DE-16-250 19 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 19 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 19 s pos_31 2013 02 DE-16-250 00 s hd2020 2013 02 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 02 DE-16-250 02 s per_35 2013 02 DE-16-250 03 s s_14 2013 02 DE-16-250 04 p (DE-627)1450183360 Bendszus, Martin 2013 02 DE-16-250 04 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 02 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 04 s pos_32 2013 02 DE-16-250 05 p (DE-627)1450189326 Wick, Wolfgang 2013 02 DE-16-250 05 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 02 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 05 s pos_33 2013 02 DE-16-250 06 p (DE-627)1450189547 Platten, Michael 2013 02 DE-16-250 06 k (DE-627)1416468684 Neurologische Klinik 2013 02 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 06 s pos_35 2013 02 DE-16-250 07 p (DE-627)1686531702 Sanghvi, Khwab 2013 02 DE-16-250 07 k (DE-627)1416468684 Neurologische Klinik 2013 02 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 07 s pos_13
spelling	10.1038/s41467-020-14642-0 doi (DE-627)1736256467 (DE-599)KXP1736256467 (OCoLC)1341373260 DE-627 ger DE-627 rda eng Aslan, Katrin verfasserin (DE-588)122006131X (DE-627)1736266896 aut Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas Katrin Aslan, Verena Turco, Jens Blobner, Jana K. Sonner, Anna Rita Liuzzi, Nicolás Gonzalo Núñez, Donatella De Feo, Philipp Kickingereder, Manuel Fischer, Ed Green, Ahmed Sadik, Mirco Friedrich, Khwab Sanghvi, Michael Kilian, Frederik Cichon, Lara Wolf, Kristine Jähne, Anna von Landenberg, Lukas Bunse, Felix Sahm, Daniel Schrimpf, Jochen Meyer, Allen Alexander, Gianluca Brugnara, Ralph Röth, Kira Pfleiderer, Beate Niesler, Andreas von Deimling, Christiane Opitz, Michael O. Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher & Michael Platten 18 February 2020 14 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 22.10.2020 Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. Turco, Verena verfasserin aut Blobner, Jens 1991- verfasserin (DE-588)1236368029 (DE-627)1761726706 aut Sonner, Jana K. verfasserin aut Liuzzi, Anna Rita verfasserin aut Núñez, Nicolás Gonzalo verfasserin aut De Feo, Donatella verfasserin aut Vollmuth, Philipp 1987- verfasserin (DE-588)1043270086 (DE-627)771319177 (DE-576)394600738 aut Fischer, Manuel verfasserin (DE-588)1155954491 (DE-627)1018513051 (DE-576)501959688 aut Green, Ed verfasserin aut Sadik, Ahmed verfasserin aut Friedrich, Mirco verfasserin aut Sanghvi, Khwab 1990- verfasserin (DE-588)1201828864 (DE-627)1685962580 aut Kilian, Michael 1990- verfasserin (DE-588)1220319422 (DE-627)1736693255 aut Cichon, Frederik 1983- verfasserin (DE-588)1220319589 (DE-627)1736693700 aut Wolf, Lara verfasserin aut Jähne, Kristine verfasserin aut von Landenberg, Anna verfasserin aut Bunse, Lukas 1988- verfasserin (DE-588)1051941229 (DE-627)787187399 (DE-576)407600426 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Schrimpf, Daniel 1984- verfasserin (DE-588)1063355044 (DE-627)812332032 (DE-576)422629529 aut Meyer, Jochen verfasserin (DE-588)1136398953 (DE-627)89281201X (DE-576)490511716 aut Alexander, Allen verfasserin aut Brugnara, Gianluca verfasserin (DE-588)1197163123 (DE-627)1678969850 aut Röth, Ralph verfasserin (DE-588)1068410221 (DE-627)820235563 (DE-576)427767059 aut Pfleiderer, Kira verfasserin (DE-588)1220060496 (DE-627)1736264265 aut Niesler, Beate verfasserin (DE-588)1066800693 (DE-627)817949615 (DE-576)426148452 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Opitz, Christiane 1979- verfasserin (DE-588)132405121 (DE-627)522675913 (DE-576)299125041 aut Breckwoldt, Michael O. 1983- verfasserin (DE-588)1022496298 (DE-627)716993392 (DE-576)365498297 aut Heiland, Sabine verfasserin (DE-588)106732626X (DE-627)818624450 (DE-576)426561368 aut Bendszus, Martin verfasserin (DE-588)1032676426 (DE-627)738634131 (DE-576)175567697 aut Wick, Wolfgang 1970- verfasserin (DE-588)120297736 (DE-627)080586929 (DE-576)186221320 aut Becher, Burkhard verfasserin aut Platten, Michael 1971- verfasserin (DE-588)121627780 (DE-627)081431848 (DE-576)261969811 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 11(2020) Artikel-Nummer 931, 14 Seiten Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:11 year:2020 extent:14 https://doi.org/10.1038/s41467-020-14642-0 Verlag Resolving-System lizenzpflichtig Volltext https://www.nature.com/articles/s41467-020-14642-0 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 14 11(2020) Artikel-Nummer 931, 14 Seiten 2013 01 DE-16-250 3784659160 00 --%%-- --%%-- --%%-- --%%-- l01 22-10-20 2013 02 DE-16-250 3789066648 00 --%%-- --%%-- --%%-- --%%-- l02 29-10-20 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_35 2013 01 DE-16-250 03 s s_14 2013 01 DE-16-250 04 p (DE-627)1761986880 Blobner, Jens 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_3 2013 01 DE-16-250 05 p (DE-627)1477787631 Vollmuth, Philipp 2013 01 DE-16-250 05 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1571959866 Fischer, Manuel 2013 01 DE-16-250 06 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1736694766 Kilian, Michael 2013 01 DE-16-250 07 k (DE-627)1416468684 Neurologische Klinik 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_14 2013 01 DE-16-250 08 p (DE-627)1736694928 Cichon, Frederik 2013 01 DE-16-250 08 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_15 2013 01 DE-16-250 09 p (DE-627)147761074X Bunse, Lukas 2013 01 DE-16-250 09 k (DE-627)1416468684 Neurologische Klinik 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 10 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_20 2013 01 DE-16-250 11 p (DE-627)1546527052 Schrimpf, Daniel 2013 01 DE-16-250 11 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_21 2013 01 DE-16-250 12 p (DE-627)1678969923 Brugnara, Gianluca 2013 01 DE-16-250 12 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_24 2013 01 DE-16-250 13 p (DE-627)1497767520 Röth, Ralph 2013 01 DE-16-250 13 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_25 2013 01 DE-16-250 14 p (DE-627)1736264397 Pfleiderer, Kira 2013 01 DE-16-250 14 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_26 2013 01 DE-16-250 15 p (DE-627)1497767695 Niesler, Beate 2013 01 DE-16-250 15 k (DE-627)1416741429 Institut für Humangenetik 2013 01 DE-16-250 15 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_27 2013 01 DE-16-250 16 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 16 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_28 2013 01 DE-16-250 17 p (DE-627)1502169614 Opitz, Christiane 2013 01 DE-16-250 17 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_29 2013 01 DE-16-250 18 p (DE-627)156023394X Breckwoldt, Michael O. 2013 01 DE-16-250 18 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 18 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 18 s pos_30 2013 01 DE-16-250 19 p (DE-627)1496564405 Heiland, Sabine 2013 01 DE-16-250 19 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 19 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 19 s pos_31 2013 02 DE-16-250 00 s hd2020 2013 02 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 02 DE-16-250 02 s per_35 2013 02 DE-16-250 03 s s_14 2013 02 DE-16-250 04 p (DE-627)1450183360 Bendszus, Martin 2013 02 DE-16-250 04 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 02 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 04 s pos_32 2013 02 DE-16-250 05 p (DE-627)1450189326 Wick, Wolfgang 2013 02 DE-16-250 05 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 02 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 05 s pos_33 2013 02 DE-16-250 06 p (DE-627)1450189547 Platten, Michael 2013 02 DE-16-250 06 k (DE-627)1416468684 Neurologische Klinik 2013 02 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 06 s pos_35 2013 02 DE-16-250 07 p (DE-627)1686531702 Sanghvi, Khwab 2013 02 DE-16-250 07 k (DE-627)1416468684 Neurologische Klinik 2013 02 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 07 s pos_13
allfields_unstemmed	10.1038/s41467-020-14642-0 doi (DE-627)1736256467 (DE-599)KXP1736256467 (OCoLC)1341373260 DE-627 ger DE-627 rda eng Aslan, Katrin verfasserin (DE-588)122006131X (DE-627)1736266896 aut Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas Katrin Aslan, Verena Turco, Jens Blobner, Jana K. Sonner, Anna Rita Liuzzi, Nicolás Gonzalo Núñez, Donatella De Feo, Philipp Kickingereder, Manuel Fischer, Ed Green, Ahmed Sadik, Mirco Friedrich, Khwab Sanghvi, Michael Kilian, Frederik Cichon, Lara Wolf, Kristine Jähne, Anna von Landenberg, Lukas Bunse, Felix Sahm, Daniel Schrimpf, Jochen Meyer, Allen Alexander, Gianluca Brugnara, Ralph Röth, Kira Pfleiderer, Beate Niesler, Andreas von Deimling, Christiane Opitz, Michael O. Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher & Michael Platten 18 February 2020 14 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 22.10.2020 Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. Turco, Verena verfasserin aut Blobner, Jens 1991- verfasserin (DE-588)1236368029 (DE-627)1761726706 aut Sonner, Jana K. verfasserin aut Liuzzi, Anna Rita verfasserin aut Núñez, Nicolás Gonzalo verfasserin aut De Feo, Donatella verfasserin aut Vollmuth, Philipp 1987- verfasserin (DE-588)1043270086 (DE-627)771319177 (DE-576)394600738 aut Fischer, Manuel verfasserin (DE-588)1155954491 (DE-627)1018513051 (DE-576)501959688 aut Green, Ed verfasserin aut Sadik, Ahmed verfasserin aut Friedrich, Mirco verfasserin aut Sanghvi, Khwab 1990- verfasserin (DE-588)1201828864 (DE-627)1685962580 aut Kilian, Michael 1990- verfasserin (DE-588)1220319422 (DE-627)1736693255 aut Cichon, Frederik 1983- verfasserin (DE-588)1220319589 (DE-627)1736693700 aut Wolf, Lara verfasserin aut Jähne, Kristine verfasserin aut von Landenberg, Anna verfasserin aut Bunse, Lukas 1988- verfasserin (DE-588)1051941229 (DE-627)787187399 (DE-576)407600426 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Schrimpf, Daniel 1984- verfasserin (DE-588)1063355044 (DE-627)812332032 (DE-576)422629529 aut Meyer, Jochen verfasserin (DE-588)1136398953 (DE-627)89281201X (DE-576)490511716 aut Alexander, Allen verfasserin aut Brugnara, Gianluca verfasserin (DE-588)1197163123 (DE-627)1678969850 aut Röth, Ralph verfasserin (DE-588)1068410221 (DE-627)820235563 (DE-576)427767059 aut Pfleiderer, Kira verfasserin (DE-588)1220060496 (DE-627)1736264265 aut Niesler, Beate verfasserin (DE-588)1066800693 (DE-627)817949615 (DE-576)426148452 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Opitz, Christiane 1979- verfasserin (DE-588)132405121 (DE-627)522675913 (DE-576)299125041 aut Breckwoldt, Michael O. 1983- verfasserin (DE-588)1022496298 (DE-627)716993392 (DE-576)365498297 aut Heiland, Sabine verfasserin (DE-588)106732626X (DE-627)818624450 (DE-576)426561368 aut Bendszus, Martin verfasserin (DE-588)1032676426 (DE-627)738634131 (DE-576)175567697 aut Wick, Wolfgang 1970- verfasserin (DE-588)120297736 (DE-627)080586929 (DE-576)186221320 aut Becher, Burkhard verfasserin aut Platten, Michael 1971- verfasserin (DE-588)121627780 (DE-627)081431848 (DE-576)261969811 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 11(2020) Artikel-Nummer 931, 14 Seiten Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:11 year:2020 extent:14 https://doi.org/10.1038/s41467-020-14642-0 Verlag Resolving-System lizenzpflichtig Volltext https://www.nature.com/articles/s41467-020-14642-0 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 14 11(2020) Artikel-Nummer 931, 14 Seiten 2013 01 DE-16-250 3784659160 00 --%%-- --%%-- --%%-- --%%-- l01 22-10-20 2013 02 DE-16-250 3789066648 00 --%%-- --%%-- --%%-- --%%-- l02 29-10-20 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_35 2013 01 DE-16-250 03 s s_14 2013 01 DE-16-250 04 p (DE-627)1761986880 Blobner, Jens 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_3 2013 01 DE-16-250 05 p (DE-627)1477787631 Vollmuth, Philipp 2013 01 DE-16-250 05 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1571959866 Fischer, Manuel 2013 01 DE-16-250 06 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1736694766 Kilian, Michael 2013 01 DE-16-250 07 k (DE-627)1416468684 Neurologische Klinik 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_14 2013 01 DE-16-250 08 p (DE-627)1736694928 Cichon, Frederik 2013 01 DE-16-250 08 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_15 2013 01 DE-16-250 09 p (DE-627)147761074X Bunse, Lukas 2013 01 DE-16-250 09 k (DE-627)1416468684 Neurologische Klinik 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 10 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_20 2013 01 DE-16-250 11 p (DE-627)1546527052 Schrimpf, Daniel 2013 01 DE-16-250 11 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_21 2013 01 DE-16-250 12 p (DE-627)1678969923 Brugnara, Gianluca 2013 01 DE-16-250 12 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_24 2013 01 DE-16-250 13 p (DE-627)1497767520 Röth, Ralph 2013 01 DE-16-250 13 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_25 2013 01 DE-16-250 14 p (DE-627)1736264397 Pfleiderer, Kira 2013 01 DE-16-250 14 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_26 2013 01 DE-16-250 15 p (DE-627)1497767695 Niesler, Beate 2013 01 DE-16-250 15 k (DE-627)1416741429 Institut für Humangenetik 2013 01 DE-16-250 15 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_27 2013 01 DE-16-250 16 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 16 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_28 2013 01 DE-16-250 17 p (DE-627)1502169614 Opitz, Christiane 2013 01 DE-16-250 17 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_29 2013 01 DE-16-250 18 p (DE-627)156023394X Breckwoldt, Michael O. 2013 01 DE-16-250 18 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 18 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 18 s pos_30 2013 01 DE-16-250 19 p (DE-627)1496564405 Heiland, Sabine 2013 01 DE-16-250 19 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 19 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 19 s pos_31 2013 02 DE-16-250 00 s hd2020 2013 02 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 02 DE-16-250 02 s per_35 2013 02 DE-16-250 03 s s_14 2013 02 DE-16-250 04 p (DE-627)1450183360 Bendszus, Martin 2013 02 DE-16-250 04 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 02 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 04 s pos_32 2013 02 DE-16-250 05 p (DE-627)1450189326 Wick, Wolfgang 2013 02 DE-16-250 05 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 02 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 05 s pos_33 2013 02 DE-16-250 06 p (DE-627)1450189547 Platten, Michael 2013 02 DE-16-250 06 k (DE-627)1416468684 Neurologische Klinik 2013 02 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 06 s pos_35 2013 02 DE-16-250 07 p (DE-627)1686531702 Sanghvi, Khwab 2013 02 DE-16-250 07 k (DE-627)1416468684 Neurologische Klinik 2013 02 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 07 s pos_13
allfieldsGer	10.1038/s41467-020-14642-0 doi (DE-627)1736256467 (DE-599)KXP1736256467 (OCoLC)1341373260 DE-627 ger DE-627 rda eng Aslan, Katrin verfasserin (DE-588)122006131X (DE-627)1736266896 aut Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas Katrin Aslan, Verena Turco, Jens Blobner, Jana K. Sonner, Anna Rita Liuzzi, Nicolás Gonzalo Núñez, Donatella De Feo, Philipp Kickingereder, Manuel Fischer, Ed Green, Ahmed Sadik, Mirco Friedrich, Khwab Sanghvi, Michael Kilian, Frederik Cichon, Lara Wolf, Kristine Jähne, Anna von Landenberg, Lukas Bunse, Felix Sahm, Daniel Schrimpf, Jochen Meyer, Allen Alexander, Gianluca Brugnara, Ralph Röth, Kira Pfleiderer, Beate Niesler, Andreas von Deimling, Christiane Opitz, Michael O. Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher & Michael Platten 18 February 2020 14 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 22.10.2020 Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. Turco, Verena verfasserin aut Blobner, Jens 1991- verfasserin (DE-588)1236368029 (DE-627)1761726706 aut Sonner, Jana K. verfasserin aut Liuzzi, Anna Rita verfasserin aut Núñez, Nicolás Gonzalo verfasserin aut De Feo, Donatella verfasserin aut Vollmuth, Philipp 1987- verfasserin (DE-588)1043270086 (DE-627)771319177 (DE-576)394600738 aut Fischer, Manuel verfasserin (DE-588)1155954491 (DE-627)1018513051 (DE-576)501959688 aut Green, Ed verfasserin aut Sadik, Ahmed verfasserin aut Friedrich, Mirco verfasserin aut Sanghvi, Khwab 1990- verfasserin (DE-588)1201828864 (DE-627)1685962580 aut Kilian, Michael 1990- verfasserin (DE-588)1220319422 (DE-627)1736693255 aut Cichon, Frederik 1983- verfasserin (DE-588)1220319589 (DE-627)1736693700 aut Wolf, Lara verfasserin aut Jähne, Kristine verfasserin aut von Landenberg, Anna verfasserin aut Bunse, Lukas 1988- verfasserin (DE-588)1051941229 (DE-627)787187399 (DE-576)407600426 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Schrimpf, Daniel 1984- verfasserin (DE-588)1063355044 (DE-627)812332032 (DE-576)422629529 aut Meyer, Jochen verfasserin (DE-588)1136398953 (DE-627)89281201X (DE-576)490511716 aut Alexander, Allen verfasserin aut Brugnara, Gianluca verfasserin (DE-588)1197163123 (DE-627)1678969850 aut Röth, Ralph verfasserin (DE-588)1068410221 (DE-627)820235563 (DE-576)427767059 aut Pfleiderer, Kira verfasserin (DE-588)1220060496 (DE-627)1736264265 aut Niesler, Beate verfasserin (DE-588)1066800693 (DE-627)817949615 (DE-576)426148452 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Opitz, Christiane 1979- verfasserin (DE-588)132405121 (DE-627)522675913 (DE-576)299125041 aut Breckwoldt, Michael O. 1983- verfasserin (DE-588)1022496298 (DE-627)716993392 (DE-576)365498297 aut Heiland, Sabine verfasserin (DE-588)106732626X (DE-627)818624450 (DE-576)426561368 aut Bendszus, Martin verfasserin (DE-588)1032676426 (DE-627)738634131 (DE-576)175567697 aut Wick, Wolfgang 1970- verfasserin (DE-588)120297736 (DE-627)080586929 (DE-576)186221320 aut Becher, Burkhard verfasserin aut Platten, Michael 1971- verfasserin (DE-588)121627780 (DE-627)081431848 (DE-576)261969811 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 11(2020) Artikel-Nummer 931, 14 Seiten Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:11 year:2020 extent:14 https://doi.org/10.1038/s41467-020-14642-0 Verlag Resolving-System lizenzpflichtig Volltext https://www.nature.com/articles/s41467-020-14642-0 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 14 11(2020) Artikel-Nummer 931, 14 Seiten 2013 01 DE-16-250 3784659160 00 --%%-- --%%-- --%%-- --%%-- l01 22-10-20 2013 02 DE-16-250 3789066648 00 --%%-- --%%-- --%%-- --%%-- l02 29-10-20 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_35 2013 01 DE-16-250 03 s s_14 2013 01 DE-16-250 04 p (DE-627)1761986880 Blobner, Jens 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_3 2013 01 DE-16-250 05 p (DE-627)1477787631 Vollmuth, Philipp 2013 01 DE-16-250 05 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1571959866 Fischer, Manuel 2013 01 DE-16-250 06 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1736694766 Kilian, Michael 2013 01 DE-16-250 07 k (DE-627)1416468684 Neurologische Klinik 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_14 2013 01 DE-16-250 08 p (DE-627)1736694928 Cichon, Frederik 2013 01 DE-16-250 08 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_15 2013 01 DE-16-250 09 p (DE-627)147761074X Bunse, Lukas 2013 01 DE-16-250 09 k (DE-627)1416468684 Neurologische Klinik 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 10 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_20 2013 01 DE-16-250 11 p (DE-627)1546527052 Schrimpf, Daniel 2013 01 DE-16-250 11 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_21 2013 01 DE-16-250 12 p (DE-627)1678969923 Brugnara, Gianluca 2013 01 DE-16-250 12 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_24 2013 01 DE-16-250 13 p (DE-627)1497767520 Röth, Ralph 2013 01 DE-16-250 13 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_25 2013 01 DE-16-250 14 p (DE-627)1736264397 Pfleiderer, Kira 2013 01 DE-16-250 14 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_26 2013 01 DE-16-250 15 p (DE-627)1497767695 Niesler, Beate 2013 01 DE-16-250 15 k (DE-627)1416741429 Institut für Humangenetik 2013 01 DE-16-250 15 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_27 2013 01 DE-16-250 16 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 16 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_28 2013 01 DE-16-250 17 p (DE-627)1502169614 Opitz, Christiane 2013 01 DE-16-250 17 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_29 2013 01 DE-16-250 18 p (DE-627)156023394X Breckwoldt, Michael O. 2013 01 DE-16-250 18 k (DE-627)1416741267 Neurologische Universitätsklinik 2013 01 DE-16-250 18 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 18 s 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Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher & Michael Platten 18 February 2020 14 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 22.10.2020 Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. Turco, Verena verfasserin aut Blobner, Jens 1991- verfasserin (DE-588)1236368029 (DE-627)1761726706 aut Sonner, Jana K. verfasserin aut Liuzzi, Anna Rita verfasserin aut Núñez, Nicolás Gonzalo verfasserin aut De Feo, Donatella verfasserin aut Vollmuth, Philipp 1987- verfasserin (DE-588)1043270086 (DE-627)771319177 (DE-576)394600738 aut Fischer, Manuel verfasserin (DE-588)1155954491 (DE-627)1018513051 (DE-576)501959688 aut Green, Ed verfasserin aut Sadik, Ahmed verfasserin aut Friedrich, Mirco verfasserin aut Sanghvi, Khwab 1990- verfasserin (DE-588)1201828864 (DE-627)1685962580 aut Kilian, Michael 1990- verfasserin (DE-588)1220319422 (DE-627)1736693255 aut Cichon, Frederik 1983- verfasserin (DE-588)1220319589 (DE-627)1736693700 aut Wolf, Lara verfasserin aut Jähne, Kristine verfasserin aut von Landenberg, Anna verfasserin aut Bunse, Lukas 1988- verfasserin (DE-588)1051941229 (DE-627)787187399 (DE-576)407600426 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 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(DE-576)175567697 aut Wick, Wolfgang 1970- verfasserin (DE-588)120297736 (DE-627)080586929 (DE-576)186221320 aut Becher, Burkhard verfasserin aut Platten, Michael 1971- verfasserin (DE-588)121627780 (DE-627)081431848 (DE-576)261969811 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 11(2020) Artikel-Nummer 931, 14 Seiten Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:11 year:2020 extent:14 https://doi.org/10.1038/s41467-020-14642-0 Verlag Resolving-System lizenzpflichtig Volltext https://www.nature.com/articles/s41467-020-14642-0 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 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source	Enthalten in Nature Communications 11(2020) Artikel-Nummer 931, 14 Seiten volume:11 year:2020 extent:14
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authorswithroles_txt_mv	Aslan, Katrin @@aut@@ Turco, Verena @@aut@@ Blobner, Jens @@aut@@ Sonner, Jana K. @@aut@@ Liuzzi, Anna Rita @@aut@@ Núñez, Nicolás Gonzalo @@aut@@ De Feo, Donatella @@aut@@ Vollmuth, Philipp @@aut@@ Fischer, Manuel @@aut@@ Green, Ed @@aut@@ Sadik, Ahmed @@aut@@ Friedrich, Mirco @@aut@@ Sanghvi, Khwab @@aut@@ Kilian, Michael @@aut@@ Cichon, Frederik @@aut@@ Wolf, Lara @@aut@@ Jähne, Kristine @@aut@@ von Landenberg, Anna @@aut@@ Bunse, Lukas @@aut@@ Sahm, Felix @@aut@@ Schrimpf, Daniel @@aut@@ Meyer, Jochen @@aut@@ Alexander, Allen @@aut@@ Brugnara, Gianluca @@aut@@ Röth, Ralph @@aut@@ Pfleiderer, Kira @@aut@@ Niesler, Beate @@aut@@ Deimling, Andreas von @@aut@@ Opitz, Christiane @@aut@@ Breckwoldt, Michael O. @@aut@@ Heiland, Sabine @@aut@@ Bendszus, Martin @@aut@@ Wick, Wolfgang @@aut@@ Becher, Burkhard @@aut@@ Platten, Michael @@aut@@
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Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Turco, Verena</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Blobner, Jens</subfield><subfield code="d">1991-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1236368029</subfield><subfield code="0">(DE-627)1761726706</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sonner, Jana K.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Liuzzi, Anna Rita</subfield><subfield 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code="0">(DE-627)1416741267</subfield><subfield code="a">Neurologische Universitätsklinik</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">06</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">06</subfield><subfield code="s">s</subfield><subfield code="a">pos_9</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">07</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1736694766</subfield><subfield code="a">Kilian, Michael</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">07</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416468684</subfield><subfield code="a">Neurologische Klinik</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">07</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">07</subfield><subfield code="s">s</subfield><subfield code="a">pos_14</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">08</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1736694928</subfield><subfield code="a">Cichon, Frederik</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">08</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416535500</subfield><subfield code="a">Fakultät für Biowissenschaften</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">08</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">08</subfield><subfield code="s">s</subfield><subfield code="a">pos_15</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">09</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)147761074X</subfield><subfield code="a">Bunse, Lukas</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">09</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416468684</subfield><subfield code="a">Neurologische Klinik</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">09</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">09</subfield><subfield code="s">s</subfield><subfield code="a">pos_19</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">10</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)143607634X</subfield><subfield code="a">Sahm, Felix</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">10</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416741658</subfield><subfield code="a">Pathologisches Institut</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield 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code="s">s</subfield><subfield code="a">pos_21</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">12</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1678969923</subfield><subfield code="a">Brugnara, Gianluca</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">12</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416741267</subfield><subfield code="a">Neurologische Universitätsklinik</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">12</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">12</subfield><subfield code="s">s</subfield><subfield code="a">pos_24</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">13</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1497767520</subfield><subfield code="a">Röth, Ralph</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">13</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416466967</subfield><subfield code="a">Medizinische Fakultät Heidelberg</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">13</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">13</subfield><subfield code="s">s</subfield><subfield code="a">pos_25</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">14</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1736264397</subfield><subfield code="a">Pfleiderer, Kira</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">14</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416466967</subfield><subfield code="a">Medizinische Fakultät Heidelberg</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">14</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">14</subfield><subfield code="s">s</subfield><subfield code="a">pos_26</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">15</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1497767695</subfield><subfield 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code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">15</subfield><subfield code="s">s</subfield><subfield code="a">pos_27</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">16</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1448137985</subfield><subfield code="a">Deimling, Andreas von</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">16</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416741658</subfield><subfield code="a">Pathologisches Institut</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">16</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">16</subfield><subfield code="s">s</subfield><subfield code="a">pos_28</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">17</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1502169614</subfield><subfield code="a">Opitz, Christiane</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">17</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416741267</subfield><subfield code="a">Neurologische Universitätsklinik</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">17</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">17</subfield><subfield code="s">s</subfield><subfield code="a">pos_29</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">18</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)156023394X</subfield><subfield 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code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">19</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1496564405</subfield><subfield code="a">Heiland, Sabine</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">19</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416741267</subfield><subfield code="a">Neurologische Universitätsklinik</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">19</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410501914</subfield><subfield code="a">Verfasser</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">01</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">19</subfield><subfield code="s">s</subfield><subfield code="a">pos_31</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">02</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">00</subfield><subfield code="s">s</subfield><subfield code="a">hd2020</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">02</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">01</subfield><subfield code="s">s</subfield><subfield code="0">(DE-627)1410508463</subfield><subfield code="a">wissenschaftlicher Artikel (Zeitschrift)</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">02</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">02</subfield><subfield code="s">s</subfield><subfield code="a">per_35</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">02</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">03</subfield><subfield code="s">s</subfield><subfield code="a">s_14</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">02</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">04</subfield><subfield code="s">p</subfield><subfield code="0">(DE-627)1450183360</subfield><subfield code="a">Bendszus, Martin</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield code="2">2013</subfield><subfield code="1">02</subfield><subfield code="x">DE-16-250</subfield><subfield code="8">04</subfield><subfield code="s">k</subfield><subfield code="0">(DE-627)1416741267</subfield><subfield code="a">Neurologische Universitätsklinik</subfield></datafield><datafield tag="982" ind1=" " ind2=" "><subfield 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Sonner, Anna Rita Liuzzi, Nicolás Gonzalo Núñez, Donatella De Feo, Philipp Kickingereder, Manuel Fischer, Ed Green, Ahmed Sadik, Mirco Friedrich, Khwab Sanghvi, Michael Kilian, Frederik Cichon, Lara Wolf, Kristine Jähne, Anna von Landenberg, Lukas Bunse, Felix Sahm, Daniel Schrimpf, Jochen Meyer, Allen Alexander, Gianluca Brugnara, Ralph Röth, Kira Pfleiderer, Beate Niesler, Andreas von Deimling, Christiane Opitz, Michael O. Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher & Michael Platten
topic	2013 hd2020 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_35 2013 s_14 2013 Blobner, Jens 2013 Medizinische Fakultät Heidelberg 2013 Verfasser 2013 pos_3 2013 Vollmuth, Philipp 2013 Neurologische Universitätsklinik 2013 pos_8 2013 Fischer, Manuel 2013 pos_9 2013 Kilian, Michael 2013 Neurologische Klinik 2013 pos_14 2013 Cichon, Frederik 2013 Fakultät für Biowissenschaften 2013 pos_15 2013 Bunse, Lukas 2013 pos_19 2013 Sahm, Felix 2013 Pathologisches Institut 2013 pos_20 2013 Schrimpf, Daniel 2013 pos_21 2013 Brugnara, Gianluca 2013 pos_24 2013 Röth, Ralph 2013 pos_25 2013 Pfleiderer, Kira 2013 pos_26 2013 Niesler, Beate 2013 Institut für Humangenetik 2013 pos_27 2013 Deimling, Andreas von 2013 pos_28 2013 Opitz, Christiane 2013 pos_29 2013 Breckwoldt, Michael O. 2013 pos_30 2013 Heiland, Sabine 2013 pos_31 2013 Bendszus, Martin 2013 pos_32 2013 Wick, Wolfgang 2013 pos_33 2013 Platten, Michael 2013 pos_35 2013 Sanghvi, Khwab 2013 pos_13
topic_unstemmed	2013 hd2020 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_35 2013 s_14 2013 Blobner, Jens 2013 Medizinische Fakultät Heidelberg 2013 Verfasser 2013 pos_3 2013 Vollmuth, Philipp 2013 Neurologische Universitätsklinik 2013 pos_8 2013 Fischer, Manuel 2013 pos_9 2013 Kilian, Michael 2013 Neurologische Klinik 2013 pos_14 2013 Cichon, Frederik 2013 Fakultät für Biowissenschaften 2013 pos_15 2013 Bunse, Lukas 2013 pos_19 2013 Sahm, Felix 2013 Pathologisches Institut 2013 pos_20 2013 Schrimpf, Daniel 2013 pos_21 2013 Brugnara, Gianluca 2013 pos_24 2013 Röth, Ralph 2013 pos_25 2013 Pfleiderer, Kira 2013 pos_26 2013 Niesler, Beate 2013 Institut für Humangenetik 2013 pos_27 2013 Deimling, Andreas von 2013 pos_28 2013 Opitz, Christiane 2013 pos_29 2013 Breckwoldt, Michael O. 2013 pos_30 2013 Heiland, Sabine 2013 pos_31 2013 Bendszus, Martin 2013 pos_32 2013 Wick, Wolfgang 2013 pos_33 2013 Platten, Michael 2013 pos_35 2013 Sanghvi, Khwab 2013 pos_13
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title	Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas
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title_full	Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas Katrin Aslan, Verena Turco, Jens Blobner, Jana K. Sonner, Anna Rita Liuzzi, Nicolás Gonzalo Núñez, Donatella De Feo, Philipp Kickingereder, Manuel Fischer, Ed Green, Ahmed Sadik, Mirco Friedrich, Khwab Sanghvi, Michael Kilian, Frederik Cichon, Lara Wolf, Kristine Jähne, Anna von Landenberg, Lukas Bunse, Felix Sahm, Daniel Schrimpf, Jochen Meyer, Allen Alexander, Gianluca Brugnara, Ralph Röth, Kira Pfleiderer, Beate Niesler, Andreas von Deimling, Christiane Opitz, Michael O. Breckwoldt, Sabine Heiland, Martin Bendszus, Wolfgang Wick, Burkhard Becher & Michael Platten
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title_sort	heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas
title_auth	Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas
abstract	Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. Gesehen am 22.10.2020
abstractGer	Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. Gesehen am 22.10.2020
abstract_unstemmed	Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. Gesehen am 22.10.2020
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title_short	Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas
url	https://doi.org/10.1038/s41467-020-14642-0 https://www.nature.com/articles/s41467-020-14642-0
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author2Str	Turco, Verena Blobner, Jens 1991- Sonner, Jana K. Liuzzi, Anna Rita Núñez, Nicolás Gonzalo De Feo, Donatella Vollmuth, Philipp 1987- Fischer, Manuel Green, Ed Sadik, Ahmed Friedrich, Mirco Sanghvi, Khwab 1990- Kilian, Michael 1990- Cichon, Frederik 1983- Wolf, Lara Jähne, Kristine von Landenberg, Anna Bunse, Lukas 1988- Sahm, Felix 1984- Schrimpf, Daniel 1984- Meyer, Jochen Alexander, Allen Brugnara, Gianluca Röth, Ralph Pfleiderer, Kira Niesler, Beate Deimling, Andreas von 1959- Opitz, Christiane 1979- Breckwoldt, Michael O. 1983- Heiland, Sabine Bendszus, Martin Wick, Wolfgang 1970- Becher, Burkhard Platten, Michael 1971-
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up_date	2024-07-04T18:38:16.104Z
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Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas

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