Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much l...
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Autor*in:	Hridesh Banerjee [verfasserIn] Hector Nieves-Rosado [verfasserIn] Aditi Kulkarni [verfasserIn] Benjamin Murter [verfasserIn] Kyle V. McGrath [verfasserIn] Uma R. Chandran [verfasserIn] Alexander Chang [verfasserIn] Andrea L. Szymczak-Workman [verfasserIn] Lazar Vujanovic [verfasserIn] Greg M. Delgoffe [verfasserIn] Robert L. Ferris [verfasserIn] Lawrence P. Kane [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	regulatory T cells (Treg) T cell immunoglobulin and mucin 3 (Tim-3) cellular signaling cellular metabolism tumor immunology immunosuppression

Übergeordnetes Werk:	In: Cell Reports - Elsevier, 2015, 36(2021), 11, Seite 109699-
Übergeordnetes Werk:	volume:36 ; year:2021 ; number:11 ; pages:109699-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.celrep.2021.109699

Katalog-ID:	DOAJ005220769

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245	1	0	\|a Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment
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520			\|a Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer.
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650		4	\|a tumor immunology
650		4	\|a immunosuppression
653		0	\|a Biology (General)
700	0		\|a Hector Nieves-Rosado \|e verfasserin \|4 aut
700	0		\|a Aditi Kulkarni \|e verfasserin \|4 aut
700	0		\|a Benjamin Murter \|e verfasserin \|4 aut
700	0		\|a Kyle V. McGrath \|e verfasserin \|4 aut
700	0		\|a Uma R. Chandran \|e verfasserin \|4 aut
700	0		\|a Alexander Chang \|e verfasserin \|4 aut
700	0		\|a Andrea L. Szymczak-Workman \|e verfasserin \|4 aut
700	0		\|a Lazar Vujanovic \|e verfasserin \|4 aut
700	0		\|a Greg M. Delgoffe \|e verfasserin \|4 aut
700	0		\|a Robert L. Ferris \|e verfasserin \|4 aut
700	0		\|a Lawrence P. Kane \|e verfasserin \|4 aut
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publishDate	2021
allfields	10.1016/j.celrep.2021.109699 doi (DE-627)DOAJ005220769 (DE-599)DOAJ44dc63899c1d47c7bb8e826cd9767e89 DE-627 ger DE-627 rakwb eng QH301-705.5 Hridesh Banerjee verfasserin aut Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer. regulatory T cells (Treg) T cell immunoglobulin and mucin 3 (Tim-3) cellular signaling cellular metabolism tumor immunology immunosuppression Biology (General) Hector Nieves-Rosado verfasserin aut Aditi Kulkarni verfasserin aut Benjamin Murter verfasserin aut Kyle V. McGrath verfasserin aut Uma R. Chandran verfasserin aut Alexander Chang verfasserin aut Andrea L. Szymczak-Workman verfasserin aut Lazar Vujanovic verfasserin aut Greg M. Delgoffe verfasserin aut Robert L. Ferris verfasserin aut Lawrence P. Kane verfasserin aut In Cell Reports Elsevier, 2015 36(2021), 11, Seite 109699- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:36 year:2021 number:11 pages:109699- https://doi.org/10.1016/j.celrep.2021.109699 kostenfrei https://doaj.org/article/44dc63899c1d47c7bb8e826cd9767e89 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721011463 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 36 2021 11 109699-
spelling	10.1016/j.celrep.2021.109699 doi (DE-627)DOAJ005220769 (DE-599)DOAJ44dc63899c1d47c7bb8e826cd9767e89 DE-627 ger DE-627 rakwb eng QH301-705.5 Hridesh Banerjee verfasserin aut Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer. regulatory T cells (Treg) T cell immunoglobulin and mucin 3 (Tim-3) cellular signaling cellular metabolism tumor immunology immunosuppression Biology (General) Hector Nieves-Rosado verfasserin aut Aditi Kulkarni verfasserin aut Benjamin Murter verfasserin aut Kyle V. McGrath verfasserin aut Uma R. Chandran verfasserin aut Alexander Chang verfasserin aut Andrea L. Szymczak-Workman verfasserin aut Lazar Vujanovic verfasserin aut Greg M. Delgoffe verfasserin aut Robert L. Ferris verfasserin aut Lawrence P. Kane verfasserin aut In Cell Reports Elsevier, 2015 36(2021), 11, Seite 109699- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:36 year:2021 number:11 pages:109699- https://doi.org/10.1016/j.celrep.2021.109699 kostenfrei https://doaj.org/article/44dc63899c1d47c7bb8e826cd9767e89 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721011463 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 36 2021 11 109699-
allfields_unstemmed	10.1016/j.celrep.2021.109699 doi (DE-627)DOAJ005220769 (DE-599)DOAJ44dc63899c1d47c7bb8e826cd9767e89 DE-627 ger DE-627 rakwb eng QH301-705.5 Hridesh Banerjee verfasserin aut Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer. regulatory T cells (Treg) T cell immunoglobulin and mucin 3 (Tim-3) cellular signaling cellular metabolism tumor immunology immunosuppression Biology (General) Hector Nieves-Rosado verfasserin aut Aditi Kulkarni verfasserin aut Benjamin Murter verfasserin aut Kyle V. McGrath verfasserin aut Uma R. Chandran verfasserin aut Alexander Chang verfasserin aut Andrea L. Szymczak-Workman verfasserin aut Lazar Vujanovic verfasserin aut Greg M. Delgoffe verfasserin aut Robert L. Ferris verfasserin aut Lawrence P. Kane verfasserin aut In Cell Reports Elsevier, 2015 36(2021), 11, Seite 109699- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:36 year:2021 number:11 pages:109699- https://doi.org/10.1016/j.celrep.2021.109699 kostenfrei https://doaj.org/article/44dc63899c1d47c7bb8e826cd9767e89 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721011463 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 36 2021 11 109699-
allfieldsGer	10.1016/j.celrep.2021.109699 doi (DE-627)DOAJ005220769 (DE-599)DOAJ44dc63899c1d47c7bb8e826cd9767e89 DE-627 ger DE-627 rakwb eng QH301-705.5 Hridesh Banerjee verfasserin aut Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer. regulatory T cells (Treg) T cell immunoglobulin and mucin 3 (Tim-3) cellular signaling cellular metabolism tumor immunology immunosuppression Biology (General) Hector Nieves-Rosado verfasserin aut Aditi Kulkarni verfasserin aut Benjamin Murter verfasserin aut Kyle V. McGrath verfasserin aut Uma R. Chandran verfasserin aut Alexander Chang verfasserin aut Andrea L. Szymczak-Workman verfasserin aut Lazar Vujanovic verfasserin aut Greg M. Delgoffe verfasserin aut Robert L. Ferris verfasserin aut Lawrence P. Kane verfasserin aut In Cell Reports Elsevier, 2015 36(2021), 11, Seite 109699- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:36 year:2021 number:11 pages:109699- https://doi.org/10.1016/j.celrep.2021.109699 kostenfrei https://doaj.org/article/44dc63899c1d47c7bb8e826cd9767e89 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721011463 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 36 2021 11 109699-
allfieldsSound	10.1016/j.celrep.2021.109699 doi (DE-627)DOAJ005220769 (DE-599)DOAJ44dc63899c1d47c7bb8e826cd9767e89 DE-627 ger DE-627 rakwb eng QH301-705.5 Hridesh Banerjee verfasserin aut Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer. regulatory T cells (Treg) T cell immunoglobulin and mucin 3 (Tim-3) cellular signaling cellular metabolism tumor immunology immunosuppression Biology (General) Hector Nieves-Rosado verfasserin aut Aditi Kulkarni verfasserin aut Benjamin Murter verfasserin aut Kyle V. McGrath verfasserin aut Uma R. Chandran verfasserin aut Alexander Chang verfasserin aut Andrea L. Szymczak-Workman verfasserin aut Lazar Vujanovic verfasserin aut Greg M. Delgoffe verfasserin aut Robert L. Ferris verfasserin aut Lawrence P. Kane verfasserin aut In Cell Reports Elsevier, 2015 36(2021), 11, Seite 109699- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:36 year:2021 number:11 pages:109699- https://doi.org/10.1016/j.celrep.2021.109699 kostenfrei https://doaj.org/article/44dc63899c1d47c7bb8e826cd9767e89 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124721011463 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 36 2021 11 109699-
language	English
source	In Cell Reports 36(2021), 11, Seite 109699- volume:36 year:2021 number:11 pages:109699-
sourceStr	In Cell Reports 36(2021), 11, Seite 109699- volume:36 year:2021 number:11 pages:109699-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	regulatory T cells (Treg) T cell immunoglobulin and mucin 3 (Tim-3) cellular signaling cellular metabolism tumor immunology immunosuppression Biology (General)
isfreeaccess_bool	true
container_title	Cell Reports
authorswithroles_txt_mv	Hridesh Banerjee @@aut@@ Hector Nieves-Rosado @@aut@@ Aditi Kulkarni @@aut@@ Benjamin Murter @@aut@@ Kyle V. McGrath @@aut@@ Uma R. Chandran @@aut@@ Alexander Chang @@aut@@ Andrea L. Szymczak-Workman @@aut@@ Lazar Vujanovic @@aut@@ Greg M. Delgoffe @@aut@@ Robert L. Ferris @@aut@@ Lawrence P. Kane @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	684964562
id	DOAJ005220769
language_de	englisch
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callnumber-first	Q - Science
author	Hridesh Banerjee
spellingShingle	Hridesh Banerjee misc QH301-705.5 misc regulatory T cells (Treg) misc T cell immunoglobulin and mucin 3 (Tim-3) misc cellular signaling misc cellular metabolism misc tumor immunology misc immunosuppression misc Biology (General) Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment
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topic_title	QH301-705.5 Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment regulatory T cells (Treg) T cell immunoglobulin and mucin 3 (Tim-3) cellular signaling cellular metabolism tumor immunology immunosuppression
topic	misc QH301-705.5 misc regulatory T cells (Treg) misc T cell immunoglobulin and mucin 3 (Tim-3) misc cellular signaling misc cellular metabolism misc tumor immunology misc immunosuppression misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc regulatory T cells (Treg) misc T cell immunoglobulin and mucin 3 (Tim-3) misc cellular signaling misc cellular metabolism misc tumor immunology misc immunosuppression misc Biology (General)
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title	Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment
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title_full	Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment
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author_browse	Hridesh Banerjee Hector Nieves-Rosado Aditi Kulkarni Benjamin Murter Kyle V. McGrath Uma R. Chandran Alexander Chang Andrea L. Szymczak-Workman Lazar Vujanovic Greg M. Delgoffe Robert L. Ferris Lawrence P. Kane
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title_sort	expression of tim-3 drives phenotypic and functional changes in treg cells in secondary lymphoid organs and the tumor microenvironment
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title_auth	Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment
abstract	Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer.
abstractGer	Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer.
abstract_unstemmed	Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer.
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title_short	Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment
url	https://doi.org/10.1016/j.celrep.2021.109699 https://doaj.org/article/44dc63899c1d47c7bb8e826cd9767e89 http://www.sciencedirect.com/science/article/pii/S2211124721011463 https://doaj.org/toc/2211-1247
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author2	Hector Nieves-Rosado Aditi Kulkarni Benjamin Murter Kyle V. McGrath Uma R. Chandran Alexander Chang Andrea L. Szymczak-Workman Lazar Vujanovic Greg M. Delgoffe Robert L. Ferris Lawrence P. Kane
author2Str	Hector Nieves-Rosado Aditi Kulkarni Benjamin Murter Kyle V. McGrath Uma R. Chandran Alexander Chang Andrea L. Szymczak-Workman Lazar Vujanovic Greg M. Delgoffe Robert L. Ferris Lawrence P. Kane
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Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

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