Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma
Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305)....
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E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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In: Cell Reports - Elsevier, 2015, 31(2020), 5, Seite - |
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| Übergeordnetes Werk: |
volume:31 ; year:2020 ; number:5 ; pages:- |
| Links: |
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| DOI / URN: |
10.1016/j.celrep.2020.107522 |
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| Katalog-ID: |
DOAJ066309840 |
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| 245 | 1 | 0 | |a Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma |
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| 520 | |a Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. | ||
| 650 | 4 | |a cysteine-protease | |
| 650 | 4 | |a cathepsin S | |
| 650 | 4 | |a follicular lymphoma | |
| 650 | 4 | |a antigen processing and presentation | |
| 650 | 4 | |a T cell activation | |
| 650 | 4 | |a immune microenvironment | |
| 653 | 0 | |a Biology (General) | |
| 700 | 0 | |a Johannes A. Hildebrand |e verfasserin |4 aut | |
| 700 | 0 | |a Sebastian Stolz |e verfasserin |4 aut | |
| 700 | 0 | |a Sarah Haebe |e verfasserin |4 aut | |
| 700 | 0 | |a Stefan Alig |e verfasserin |4 aut | |
| 700 | 0 | |a Christopher P. Trevisani |e verfasserin |4 aut | |
| 700 | 0 | |a Francisco Osorio-Barrios |e verfasserin |4 aut | |
| 700 | 0 | |a Michael D. Bartoschek |e verfasserin |4 aut | |
| 700 | 0 | |a Michael Mentz |e verfasserin |4 aut | |
| 700 | 0 | |a Alessandro Pastore |e verfasserin |4 aut | |
| 700 | 0 | |a Erik Gaitzsch |e verfasserin |4 aut | |
| 700 | 0 | |a Michael Heide |e verfasserin |4 aut | |
| 700 | 0 | |a Vindi Jurinovic |e verfasserin |4 aut | |
| 700 | 0 | |a Katharina Rautter |e verfasserin |4 aut | |
| 700 | 0 | |a Jay Gunawardana |e verfasserin |4 aut | |
| 700 | 0 | |a Muhammed B. Sabdia |e verfasserin |4 aut | |
| 700 | 0 | |a Monika Szczepanowski |e verfasserin |4 aut | |
| 700 | 0 | |a Julia Richter |e verfasserin |4 aut | |
| 700 | 0 | |a Wolfram Klapper |e verfasserin |4 aut | |
| 700 | 0 | |a Abner Louissaint, Jr. |e verfasserin |4 aut | |
| 700 | 0 | |a Christina Ludwig |e verfasserin |4 aut | |
| 700 | 0 | |a Sebastian Bultmann |e verfasserin |4 aut | |
| 700 | 0 | |a Heinrich Leonhardt |e verfasserin |4 aut | |
| 700 | 0 | |a Sebastian Eustermann |e verfasserin |4 aut | |
| 700 | 0 | |a Karl-Peter Hopfner |e verfasserin |4 aut | |
| 700 | 0 | |a Wolfgang Hiddemann |e verfasserin |4 aut | |
| 700 | 0 | |a Michael von Bergwelt-Baildon |e verfasserin |4 aut | |
| 700 | 0 | |a Christian Steidl |e verfasserin |4 aut | |
| 700 | 0 | |a Robert Kridel |e verfasserin |4 aut | |
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| 700 | 0 | |a Martina Rudelius |e verfasserin |4 aut | |
| 700 | 0 | |a Verena Passerini |e verfasserin |4 aut | |
| 700 | 0 | |a Josef Mautner |e verfasserin |4 aut | |
| 700 | 0 | |a Oliver Weigert |e verfasserin |4 aut | |
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10.1016/j.celrep.2020.107522 doi (DE-627)DOAJ066309840 (DE-599)DOAJ0a5e722ca6e94029b574353537c7475f DE-627 ger DE-627 rakwb eng QH301-705.5 Deepak Bararia verfasserin aut Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. cysteine-protease cathepsin S follicular lymphoma antigen processing and presentation T cell activation immune microenvironment Biology (General) Johannes A. Hildebrand verfasserin aut Sebastian Stolz verfasserin aut Sarah Haebe verfasserin aut Stefan Alig verfasserin aut Christopher P. Trevisani verfasserin aut Francisco Osorio-Barrios verfasserin aut Michael D. Bartoschek verfasserin aut Michael Mentz verfasserin aut Alessandro Pastore verfasserin aut Erik Gaitzsch verfasserin aut Michael Heide verfasserin aut Vindi Jurinovic verfasserin aut Katharina Rautter verfasserin aut Jay Gunawardana verfasserin aut Muhammed B. Sabdia verfasserin aut Monika Szczepanowski verfasserin aut Julia Richter verfasserin aut Wolfram Klapper verfasserin aut Abner Louissaint, Jr. verfasserin aut Christina Ludwig verfasserin aut Sebastian Bultmann verfasserin aut Heinrich Leonhardt verfasserin aut Sebastian Eustermann verfasserin aut Karl-Peter Hopfner verfasserin aut Wolfgang Hiddemann verfasserin aut Michael von Bergwelt-Baildon verfasserin aut Christian Steidl verfasserin aut Robert Kridel verfasserin aut Joshua W.D. Tobin verfasserin aut Maher K. Gandhi verfasserin aut David M. Weinstock verfasserin aut Marc Schmidt-Supprian verfasserin aut Menyhárt B. Sárosi verfasserin aut Martina Rudelius verfasserin aut Verena Passerini verfasserin aut Josef Mautner verfasserin aut Oliver Weigert verfasserin aut In Cell Reports Elsevier, 2015 31(2020), 5, Seite - (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:31 year:2020 number:5 pages:- https://doi.org/10.1016/j.celrep.2020.107522 kostenfrei https://doaj.org/article/0a5e722ca6e94029b574353537c7475f kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124720304228 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 31 2020 5 - |
| spelling |
10.1016/j.celrep.2020.107522 doi (DE-627)DOAJ066309840 (DE-599)DOAJ0a5e722ca6e94029b574353537c7475f DE-627 ger DE-627 rakwb eng QH301-705.5 Deepak Bararia verfasserin aut Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. cysteine-protease cathepsin S follicular lymphoma antigen processing and presentation T cell activation immune microenvironment Biology (General) Johannes A. Hildebrand verfasserin aut Sebastian Stolz verfasserin aut Sarah Haebe verfasserin aut Stefan Alig verfasserin aut Christopher P. Trevisani verfasserin aut Francisco Osorio-Barrios verfasserin aut Michael D. Bartoschek verfasserin aut Michael Mentz verfasserin aut Alessandro Pastore verfasserin aut Erik Gaitzsch verfasserin aut Michael Heide verfasserin aut Vindi Jurinovic verfasserin aut Katharina Rautter verfasserin aut Jay Gunawardana verfasserin aut Muhammed B. Sabdia verfasserin aut Monika Szczepanowski verfasserin aut Julia Richter verfasserin aut Wolfram Klapper verfasserin aut Abner Louissaint, Jr. verfasserin aut Christina Ludwig verfasserin aut Sebastian Bultmann verfasserin aut Heinrich Leonhardt verfasserin aut Sebastian Eustermann verfasserin aut Karl-Peter Hopfner verfasserin aut Wolfgang Hiddemann verfasserin aut Michael von Bergwelt-Baildon verfasserin aut Christian Steidl verfasserin aut Robert Kridel verfasserin aut Joshua W.D. Tobin verfasserin aut Maher K. Gandhi verfasserin aut David M. Weinstock verfasserin aut Marc Schmidt-Supprian verfasserin aut Menyhárt B. Sárosi verfasserin aut Martina Rudelius verfasserin aut Verena Passerini verfasserin aut Josef Mautner verfasserin aut Oliver Weigert verfasserin aut In Cell Reports Elsevier, 2015 31(2020), 5, Seite - (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:31 year:2020 number:5 pages:- https://doi.org/10.1016/j.celrep.2020.107522 kostenfrei https://doaj.org/article/0a5e722ca6e94029b574353537c7475f kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124720304228 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 31 2020 5 - |
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10.1016/j.celrep.2020.107522 doi (DE-627)DOAJ066309840 (DE-599)DOAJ0a5e722ca6e94029b574353537c7475f DE-627 ger DE-627 rakwb eng QH301-705.5 Deepak Bararia verfasserin aut Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. cysteine-protease cathepsin S follicular lymphoma antigen processing and presentation T cell activation immune microenvironment Biology (General) Johannes A. Hildebrand verfasserin aut Sebastian Stolz verfasserin aut Sarah Haebe verfasserin aut Stefan Alig verfasserin aut Christopher P. Trevisani verfasserin aut Francisco Osorio-Barrios verfasserin aut Michael D. Bartoschek verfasserin aut Michael Mentz verfasserin aut Alessandro Pastore verfasserin aut Erik Gaitzsch verfasserin aut Michael Heide verfasserin aut Vindi Jurinovic verfasserin aut Katharina Rautter verfasserin aut Jay Gunawardana verfasserin aut Muhammed B. Sabdia verfasserin aut Monika Szczepanowski verfasserin aut Julia Richter verfasserin aut Wolfram Klapper verfasserin aut Abner Louissaint, Jr. verfasserin aut Christina Ludwig verfasserin aut Sebastian Bultmann verfasserin aut Heinrich Leonhardt verfasserin aut Sebastian Eustermann verfasserin aut Karl-Peter Hopfner verfasserin aut Wolfgang Hiddemann verfasserin aut Michael von Bergwelt-Baildon verfasserin aut Christian Steidl verfasserin aut Robert Kridel verfasserin aut Joshua W.D. Tobin verfasserin aut Maher K. Gandhi verfasserin aut David M. Weinstock verfasserin aut Marc Schmidt-Supprian verfasserin aut Menyhárt B. Sárosi verfasserin aut Martina Rudelius verfasserin aut Verena Passerini verfasserin aut Josef Mautner verfasserin aut Oliver Weigert verfasserin aut In Cell Reports Elsevier, 2015 31(2020), 5, Seite - (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:31 year:2020 number:5 pages:- https://doi.org/10.1016/j.celrep.2020.107522 kostenfrei https://doaj.org/article/0a5e722ca6e94029b574353537c7475f kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124720304228 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 31 2020 5 - |
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10.1016/j.celrep.2020.107522 doi (DE-627)DOAJ066309840 (DE-599)DOAJ0a5e722ca6e94029b574353537c7475f DE-627 ger DE-627 rakwb eng QH301-705.5 Deepak Bararia verfasserin aut Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. cysteine-protease cathepsin S follicular lymphoma antigen processing and presentation T cell activation immune microenvironment Biology (General) Johannes A. Hildebrand verfasserin aut Sebastian Stolz verfasserin aut Sarah Haebe verfasserin aut Stefan Alig verfasserin aut Christopher P. Trevisani verfasserin aut Francisco Osorio-Barrios verfasserin aut Michael D. Bartoschek verfasserin aut Michael Mentz verfasserin aut Alessandro Pastore verfasserin aut Erik Gaitzsch verfasserin aut Michael Heide verfasserin aut Vindi Jurinovic verfasserin aut Katharina Rautter verfasserin aut Jay Gunawardana verfasserin aut Muhammed B. Sabdia verfasserin aut Monika Szczepanowski verfasserin aut Julia Richter verfasserin aut Wolfram Klapper verfasserin aut Abner Louissaint, Jr. verfasserin aut Christina Ludwig verfasserin aut Sebastian Bultmann verfasserin aut Heinrich Leonhardt verfasserin aut Sebastian Eustermann verfasserin aut Karl-Peter Hopfner verfasserin aut Wolfgang Hiddemann verfasserin aut Michael von Bergwelt-Baildon verfasserin aut Christian Steidl verfasserin aut Robert Kridel verfasserin aut Joshua W.D. Tobin verfasserin aut Maher K. Gandhi verfasserin aut David M. Weinstock verfasserin aut Marc Schmidt-Supprian verfasserin aut Menyhárt B. Sárosi verfasserin aut Martina Rudelius verfasserin aut Verena Passerini verfasserin aut Josef Mautner verfasserin aut Oliver Weigert verfasserin aut In Cell Reports Elsevier, 2015 31(2020), 5, Seite - (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:31 year:2020 number:5 pages:- https://doi.org/10.1016/j.celrep.2020.107522 kostenfrei https://doaj.org/article/0a5e722ca6e94029b574353537c7475f kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124720304228 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 31 2020 5 - |
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10.1016/j.celrep.2020.107522 doi (DE-627)DOAJ066309840 (DE-599)DOAJ0a5e722ca6e94029b574353537c7475f DE-627 ger DE-627 rakwb eng QH301-705.5 Deepak Bararia verfasserin aut Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. cysteine-protease cathepsin S follicular lymphoma antigen processing and presentation T cell activation immune microenvironment Biology (General) Johannes A. Hildebrand verfasserin aut Sebastian Stolz verfasserin aut Sarah Haebe verfasserin aut Stefan Alig verfasserin aut Christopher P. Trevisani verfasserin aut Francisco Osorio-Barrios verfasserin aut Michael D. Bartoschek verfasserin aut Michael Mentz verfasserin aut Alessandro Pastore verfasserin aut Erik Gaitzsch verfasserin aut Michael Heide verfasserin aut Vindi Jurinovic verfasserin aut Katharina Rautter verfasserin aut Jay Gunawardana verfasserin aut Muhammed B. Sabdia verfasserin aut Monika Szczepanowski verfasserin aut Julia Richter verfasserin aut Wolfram Klapper verfasserin aut Abner Louissaint, Jr. verfasserin aut Christina Ludwig verfasserin aut Sebastian Bultmann verfasserin aut Heinrich Leonhardt verfasserin aut Sebastian Eustermann verfasserin aut Karl-Peter Hopfner verfasserin aut Wolfgang Hiddemann verfasserin aut Michael von Bergwelt-Baildon verfasserin aut Christian Steidl verfasserin aut Robert Kridel verfasserin aut Joshua W.D. Tobin verfasserin aut Maher K. Gandhi verfasserin aut David M. Weinstock verfasserin aut Marc Schmidt-Supprian verfasserin aut Menyhárt B. Sárosi verfasserin aut Martina Rudelius verfasserin aut Verena Passerini verfasserin aut Josef Mautner verfasserin aut Oliver Weigert verfasserin aut In Cell Reports Elsevier, 2015 31(2020), 5, Seite - (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:31 year:2020 number:5 pages:- https://doi.org/10.1016/j.celrep.2020.107522 kostenfrei https://doaj.org/article/0a5e722ca6e94029b574353537c7475f kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124720304228 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 31 2020 5 - |
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Deepak Bararia @@aut@@ Johannes A. Hildebrand @@aut@@ Sebastian Stolz @@aut@@ Sarah Haebe @@aut@@ Stefan Alig @@aut@@ Christopher P. Trevisani @@aut@@ Francisco Osorio-Barrios @@aut@@ Michael D. Bartoschek @@aut@@ Michael Mentz @@aut@@ Alessandro Pastore @@aut@@ Erik Gaitzsch @@aut@@ Michael Heide @@aut@@ Vindi Jurinovic @@aut@@ Katharina Rautter @@aut@@ Jay Gunawardana @@aut@@ Muhammed B. Sabdia @@aut@@ Monika Szczepanowski @@aut@@ Julia Richter @@aut@@ Wolfram Klapper @@aut@@ Abner Louissaint, Jr. @@aut@@ Christina Ludwig @@aut@@ Sebastian Bultmann @@aut@@ Heinrich Leonhardt @@aut@@ Sebastian Eustermann @@aut@@ Karl-Peter Hopfner @@aut@@ Wolfgang Hiddemann @@aut@@ Michael von Bergwelt-Baildon @@aut@@ Christian Steidl @@aut@@ Robert Kridel @@aut@@ Joshua W.D. Tobin @@aut@@ Maher K. Gandhi @@aut@@ David M. Weinstock @@aut@@ Marc Schmidt-Supprian @@aut@@ Menyhárt B. Sárosi @@aut@@ Martina Rudelius @@aut@@ Verena Passerini @@aut@@ Josef Mautner @@aut@@ Oliver Weigert @@aut@@ |
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Deepak Bararia |
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Deepak Bararia misc QH301-705.5 misc cysteine-protease misc cathepsin S misc follicular lymphoma misc antigen processing and presentation misc T cell activation misc immune microenvironment misc Biology (General) Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma |
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QH301-705.5 Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma cysteine-protease cathepsin S follicular lymphoma antigen processing and presentation T cell activation immune microenvironment |
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misc QH301-705.5 misc cysteine-protease misc cathepsin S misc follicular lymphoma misc antigen processing and presentation misc T cell activation misc immune microenvironment misc Biology (General) |
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Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma |
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Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma |
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Deepak Bararia Johannes A. Hildebrand Sebastian Stolz Sarah Haebe Stefan Alig Christopher P. Trevisani Francisco Osorio-Barrios Michael D. Bartoschek Michael Mentz Alessandro Pastore Erik Gaitzsch Michael Heide Vindi Jurinovic Katharina Rautter Jay Gunawardana Muhammed B. Sabdia Monika Szczepanowski Julia Richter Wolfram Klapper Abner Louissaint, Jr. Christina Ludwig Sebastian Bultmann Heinrich Leonhardt Sebastian Eustermann Karl-Peter Hopfner Wolfgang Hiddemann Michael von Bergwelt-Baildon Christian Steidl Robert Kridel Joshua W.D. Tobin Maher K. Gandhi David M. Weinstock Marc Schmidt-Supprian Menyhárt B. Sárosi Martina Rudelius Verena Passerini Josef Mautner Oliver Weigert |
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cathepsin s alterations induce a tumor-promoting immune microenvironment in follicular lymphoma |
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QH301-705.5 |
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Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma |
| abstract |
Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. |
| abstractGer |
Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. |
| abstract_unstemmed |
Summary: Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment. |
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| title_short |
Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma |
| url |
https://doi.org/10.1016/j.celrep.2020.107522 https://doaj.org/article/0a5e722ca6e94029b574353537c7475f http://www.sciencedirect.com/science/article/pii/S2211124720304228 https://doaj.org/toc/2211-1247 |
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Johannes A. Hildebrand Sebastian Stolz Sarah Haebe Stefan Alig Christopher P. Trevisani Francisco Osorio-Barrios Michael D. Bartoschek Michael Mentz Alessandro Pastore Erik Gaitzsch Michael Heide Vindi Jurinovic Katharina Rautter Jay Gunawardana Muhammed B. Sabdia Monika Szczepanowski Julia Richter Wolfram Klapper Abner Louissaint, Jr. Christina Ludwig Sebastian Bultmann Heinrich Leonhardt Sebastian Eustermann Karl-Peter Hopfner Wolfgang Hiddemann Michael von Bergwelt-Baildon Christian Steidl Robert Kridel Joshua W.D. Tobin Maher K. Gandhi David M. Weinstock Marc Schmidt-Supprian Menyhárt B. Sárosi Martina Rudelius Verena Passerini Josef Mautner Oliver Weigert |
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Johannes A. Hildebrand Sebastian Stolz Sarah Haebe Stefan Alig Christopher P. Trevisani Francisco Osorio-Barrios Michael D. Bartoschek Michael Mentz Alessandro Pastore Erik Gaitzsch Michael Heide Vindi Jurinovic Katharina Rautter Jay Gunawardana Muhammed B. Sabdia Monika Szczepanowski Julia Richter Wolfram Klapper Abner Louissaint, Jr. Christina Ludwig Sebastian Bultmann Heinrich Leonhardt Sebastian Eustermann Karl-Peter Hopfner Wolfgang Hiddemann Michael von Bergwelt-Baildon Christian Steidl Robert Kridel Joshua W.D. Tobin Maher K. Gandhi David M. Weinstock Marc Schmidt-Supprian Menyhárt B. Sárosi Martina Rudelius Verena Passerini Josef Mautner Oliver Weigert |
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10.1016/j.celrep.2020.107522 |
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QH301-705.5 |
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2024-07-03T19:22:14.514Z |
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| score |
7.402916 |