Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5

Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a p...
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Autor*in:	Yoko Tsukita [verfasserIn] Tatsuma Okazaki [verfasserIn] Satoru Ebihara [verfasserIn] Riyo Komatsu [verfasserIn] Mayumi Nihei [verfasserIn] Makoto Kobayashi [verfasserIn] Taizou Hirano [verfasserIn] Hisatoshi Sugiura [verfasserIn] Tsutomu Tamada [verfasserIn] Nobuyuki Tanaka [verfasserIn] Yasufumi Sato [verfasserIn] Hideo Yagita [verfasserIn] Masakazu Ichinose [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	death receptor5 immunotherapy lymphatics blood vessels tumor microenvironment

Übergeordnetes Werk:	In: OncoImmunology - Taylor & Francis Group, 2020, 8(2019), 2
Übergeordnetes Werk:	volume:8 ; year:2019 ; number:2

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1080/2162402X.2018.1543526

Katalog-ID:	DOAJ076523624

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520			\|a Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs.
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Indexfelder

author_variant	y t yt t o to s e se r k rk m n mn m k mk t h th h s hs t t tt n t nt y s ys h y hy m i mi
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allfields	10.1080/2162402X.2018.1543526 doi (DE-627)DOAJ076523624 (DE-599)DOAJa660342324a34cdda379801c8fe94cd9 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Yoko Tsukita verfasserin aut Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs. death receptor5 immunotherapy lymphatics blood vessels tumor microenvironment Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Tatsuma Okazaki verfasserin aut Satoru Ebihara verfasserin aut Riyo Komatsu verfasserin aut Mayumi Nihei verfasserin aut Makoto Kobayashi verfasserin aut Taizou Hirano verfasserin aut Hisatoshi Sugiura verfasserin aut Tsutomu Tamada verfasserin aut Nobuyuki Tanaka verfasserin aut Yasufumi Sato verfasserin aut Hideo Yagita verfasserin aut Masakazu Ichinose verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 8(2019), 2 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:8 year:2019 number:2 https://doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/article/a660342324a34cdda379801c8fe94cd9 kostenfrei http://dx.doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 2
spelling	10.1080/2162402X.2018.1543526 doi (DE-627)DOAJ076523624 (DE-599)DOAJa660342324a34cdda379801c8fe94cd9 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Yoko Tsukita verfasserin aut Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs. death receptor5 immunotherapy lymphatics blood vessels tumor microenvironment Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Tatsuma Okazaki verfasserin aut Satoru Ebihara verfasserin aut Riyo Komatsu verfasserin aut Mayumi Nihei verfasserin aut Makoto Kobayashi verfasserin aut Taizou Hirano verfasserin aut Hisatoshi Sugiura verfasserin aut Tsutomu Tamada verfasserin aut Nobuyuki Tanaka verfasserin aut Yasufumi Sato verfasserin aut Hideo Yagita verfasserin aut Masakazu Ichinose verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 8(2019), 2 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:8 year:2019 number:2 https://doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/article/a660342324a34cdda379801c8fe94cd9 kostenfrei http://dx.doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 2
allfields_unstemmed	10.1080/2162402X.2018.1543526 doi (DE-627)DOAJ076523624 (DE-599)DOAJa660342324a34cdda379801c8fe94cd9 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Yoko Tsukita verfasserin aut Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs. death receptor5 immunotherapy lymphatics blood vessels tumor microenvironment Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Tatsuma Okazaki verfasserin aut Satoru Ebihara verfasserin aut Riyo Komatsu verfasserin aut Mayumi Nihei verfasserin aut Makoto Kobayashi verfasserin aut Taizou Hirano verfasserin aut Hisatoshi Sugiura verfasserin aut Tsutomu Tamada verfasserin aut Nobuyuki Tanaka verfasserin aut Yasufumi Sato verfasserin aut Hideo Yagita verfasserin aut Masakazu Ichinose verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 8(2019), 2 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:8 year:2019 number:2 https://doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/article/a660342324a34cdda379801c8fe94cd9 kostenfrei http://dx.doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 2
allfieldsGer	10.1080/2162402X.2018.1543526 doi (DE-627)DOAJ076523624 (DE-599)DOAJa660342324a34cdda379801c8fe94cd9 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Yoko Tsukita verfasserin aut Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs. death receptor5 immunotherapy lymphatics blood vessels tumor microenvironment Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Tatsuma Okazaki verfasserin aut Satoru Ebihara verfasserin aut Riyo Komatsu verfasserin aut Mayumi Nihei verfasserin aut Makoto Kobayashi verfasserin aut Taizou Hirano verfasserin aut Hisatoshi Sugiura verfasserin aut Tsutomu Tamada verfasserin aut Nobuyuki Tanaka verfasserin aut Yasufumi Sato verfasserin aut Hideo Yagita verfasserin aut Masakazu Ichinose verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 8(2019), 2 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:8 year:2019 number:2 https://doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/article/a660342324a34cdda379801c8fe94cd9 kostenfrei http://dx.doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 2
allfieldsSound	10.1080/2162402X.2018.1543526 doi (DE-627)DOAJ076523624 (DE-599)DOAJa660342324a34cdda379801c8fe94cd9 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Yoko Tsukita verfasserin aut Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs. death receptor5 immunotherapy lymphatics blood vessels tumor microenvironment Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Tatsuma Okazaki verfasserin aut Satoru Ebihara verfasserin aut Riyo Komatsu verfasserin aut Mayumi Nihei verfasserin aut Makoto Kobayashi verfasserin aut Taizou Hirano verfasserin aut Hisatoshi Sugiura verfasserin aut Tsutomu Tamada verfasserin aut Nobuyuki Tanaka verfasserin aut Yasufumi Sato verfasserin aut Hideo Yagita verfasserin aut Masakazu Ichinose verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 8(2019), 2 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:8 year:2019 number:2 https://doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/article/a660342324a34cdda379801c8fe94cd9 kostenfrei http://dx.doi.org/10.1080/2162402X.2018.1543526 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_2014 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 2
language	English
source	In OncoImmunology 8(2019), 2 volume:8 year:2019 number:2
sourceStr	In OncoImmunology 8(2019), 2 volume:8 year:2019 number:2
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	death receptor5 immunotherapy lymphatics blood vessels tumor microenvironment Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	OncoImmunology
authorswithroles_txt_mv	Yoko Tsukita @@aut@@ Tatsuma Okazaki @@aut@@ Satoru Ebihara @@aut@@ Riyo Komatsu @@aut@@ Mayumi Nihei @@aut@@ Makoto Kobayashi @@aut@@ Taizou Hirano @@aut@@ Hisatoshi Sugiura @@aut@@ Tsutomu Tamada @@aut@@ Nobuyuki Tanaka @@aut@@ Yasufumi Sato @@aut@@ Hideo Yagita @@aut@@ Masakazu Ichinose @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	683365428
id	DOAJ076523624
language_de	englisch
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callnumber-first	R - Medicine
author	Yoko Tsukita
spellingShingle	Yoko Tsukita misc RC581-607 misc RC254-282 misc death receptor5 misc immunotherapy misc lymphatics misc blood vessels misc tumor microenvironment misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5
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topic_title	RC581-607 RC254-282 Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5 death receptor5 immunotherapy lymphatics blood vessels tumor microenvironment
topic	misc RC581-607 misc RC254-282 misc death receptor5 misc immunotherapy misc lymphatics misc blood vessels misc tumor microenvironment misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC581-607 misc RC254-282 misc death receptor5 misc immunotherapy misc lymphatics misc blood vessels misc tumor microenvironment misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC581-607 misc RC254-282 misc death receptor5 misc immunotherapy misc lymphatics misc blood vessels misc tumor microenvironment misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5
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title_full	Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5
author_sort	Yoko Tsukita
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author_browse	Yoko Tsukita Tatsuma Okazaki Satoru Ebihara Riyo Komatsu Mayumi Nihei Makoto Kobayashi Taizou Hirano Hisatoshi Sugiura Tsutomu Tamada Nobuyuki Tanaka Yasufumi Sato Hideo Yagita Masakazu Ichinose
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author-letter	Yoko Tsukita
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title_sort	beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5
callnumber	RC581-607
title_auth	Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5
abstract	Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs.
abstractGer	Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs.
abstract_unstemmed	Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs.
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title_short	Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5
url	https://doi.org/10.1080/2162402X.2018.1543526 https://doaj.org/article/a660342324a34cdda379801c8fe94cd9 http://dx.doi.org/10.1080/2162402X.2018.1543526 https://doaj.org/toc/2162-402X
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author2	Tatsuma Okazaki Satoru Ebihara Riyo Komatsu Mayumi Nihei Makoto Kobayashi Taizou Hirano Hisatoshi Sugiura Tsutomu Tamada Nobuyuki Tanaka Yasufumi Sato Hideo Yagita Masakazu Ichinose
author2Str	Tatsuma Okazaki Satoru Ebihara Riyo Komatsu Mayumi Nihei Makoto Kobayashi Taizou Hirano Hisatoshi Sugiura Tsutomu Tamada Nobuyuki Tanaka Yasufumi Sato Hideo Yagita Masakazu Ichinose
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