MERTK Acts as a costimulatory receptor on human cd8 t cells

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

MERTK Acts as a costimulatory receptor on human cd8 t cells. / Peeters, Marlies J.W.; Dulkeviciute, Donata; Draghi, Arianna; Ritter, Cathrin; Rahbech, Anne; Skadborg, Signe K.; Seremet, Tina; Simoes, Ana Micaela Carnaz; Martinenaite, Evelina; Halldorsdottir, Holmfridur R.; Andersen, Mads Hald; Olofsson, Gitte Holmen; Svane, Inge Marie; Rasmussen, Lene Juel; Met, Ozcan; Becker, Jeurgen C.; Donia, Marco; Desler, Claus; Straten, Per Thor.

In: Cancer Immunology Research, Vol. 7, No. 9, 2019, p. 1472-1484.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Peeters, MJW, Dulkeviciute, D, Draghi, A, Ritter, C, Rahbech, A, Skadborg, SK, Seremet, T, Simoes, AMC, Martinenaite, E, Halldorsdottir, HR, Andersen, MH, Olofsson, GH, Svane, IM, Rasmussen, LJ, Met, O, Becker, JC, Donia, M, Desler, C & Straten, PT 2019, 'MERTK Acts as a costimulatory receptor on human cd8 t cells', Cancer Immunology Research, vol. 7, no. 9, pp. 1472-1484. https://doi.org/10.1158/2326-6066.CIR-18-0841

APA

Peeters, M. J. W., Dulkeviciute, D., Draghi, A., Ritter, C., Rahbech, A., Skadborg, S. K., Seremet, T., Simoes, A. M. C., Martinenaite, E., Halldorsdottir, H. R., Andersen, M. H., Olofsson, G. H., Svane, I. M., Rasmussen, L. J., Met, O., Becker, J. C., Donia, M., Desler, C., & Straten, P. T. (2019). MERTK Acts as a costimulatory receptor on human cd8 t cells. Cancer Immunology Research, 7(9), 1472-1484. https://doi.org/10.1158/2326-6066.CIR-18-0841

Vancouver

Peeters MJW, Dulkeviciute D, Draghi A, Ritter C, Rahbech A, Skadborg SK et al. MERTK Acts as a costimulatory receptor on human cd8 t cells. Cancer Immunology Research. 2019;7(9):1472-1484. https://doi.org/10.1158/2326-6066.CIR-18-0841

Author

Peeters, Marlies J.W. ; Dulkeviciute, Donata ; Draghi, Arianna ; Ritter, Cathrin ; Rahbech, Anne ; Skadborg, Signe K. ; Seremet, Tina ; Simoes, Ana Micaela Carnaz ; Martinenaite, Evelina ; Halldorsdottir, Holmfridur R. ; Andersen, Mads Hald ; Olofsson, Gitte Holmen ; Svane, Inge Marie ; Rasmussen, Lene Juel ; Met, Ozcan ; Becker, Jeurgen C. ; Donia, Marco ; Desler, Claus ; Straten, Per Thor. / MERTK Acts as a costimulatory receptor on human cd8 t cells. In: Cancer Immunology Research. 2019 ; Vol. 7, No. 9. pp. 1472-1484.

Bibtex

@article{57ced68020b443d3aa5e907278c2d51d,
title = "MERTK Acts as a costimulatory receptor on human cd8 t cells",
abstract = "The TAM family of receptor tyrosine kinases (TYRO3, AXL, and MERTK) is known to be expressed on antigen-presenting cells and function as oncogenic drivers and as inhibitors of inflammatory responses. Both human and mouse CD8 T cells are thought to be negative for TAM receptor expression. In this study, we show that T-cell receptor (TCR)-activated human primary CD8 T cells expressed MERTK and the ligand PROS1 from day 2 postactivation. PROS1-mediated MERTK signaling served as a late costimulatory signal, increasing proliferation and secretion of effector and memory- associated cytokines. Knockdown and inhibition studies confirmed that this costimulatory effect was mediated through MERTK. Transcriptomic and metabolic analyses of PROS1-blocked CD8 T cells demonstrated a role of the PROS1-MERTK axis in differentiation of memory CD8 T cells. Finally, using tumor-infiltrating lymphocytes (TIL) from melanoma patients, we show that MERTK signaling on T cells improved TIL expansion and TIL-mediated autologous cancer cell killing. We conclude that MERTK serves as a late costimulatory signal for CD8 T cells. Identification of this costimulatory function of MERTK on human CD8 T cells suggests caution in the development of MERTK inhibitors for hematologic or solid cancer treatment.",
author = "Peeters, {Marlies J.W.} and Donata Dulkeviciute and Arianna Draghi and Cathrin Ritter and Anne Rahbech and Skadborg, {Signe K.} and Tina Seremet and Simoes, {Ana Micaela Carnaz} and Evelina Martinenaite and Halldorsdottir, {Holmfridur R.} and Andersen, {Mads Hald} and Olofsson, {Gitte Holmen} and Svane, {Inge Marie} and Rasmussen, {Lene Juel} and Ozcan Met and Becker, {Jeurgen C.} and Marco Donia and Claus Desler and Straten, {Per Thor}",
year = "2019",
doi = "10.1158/2326-6066.CIR-18-0841",
language = "English",
volume = "7",
pages = "1472--1484",
journal = "Cancer Immunology Research",
issn = "2326-6066",
publisher = "American Association for Cancer Research",
number = "9",

}

RIS

TY - JOUR

T1 - MERTK Acts as a costimulatory receptor on human cd8 t cells

AU - Peeters, Marlies J.W.

AU - Dulkeviciute, Donata

AU - Draghi, Arianna

AU - Ritter, Cathrin

AU - Rahbech, Anne

AU - Skadborg, Signe K.

AU - Seremet, Tina

AU - Simoes, Ana Micaela Carnaz

AU - Martinenaite, Evelina

AU - Halldorsdottir, Holmfridur R.

AU - Andersen, Mads Hald

AU - Olofsson, Gitte Holmen

AU - Svane, Inge Marie

AU - Rasmussen, Lene Juel

AU - Met, Ozcan

AU - Becker, Jeurgen C.

AU - Donia, Marco

AU - Desler, Claus

AU - Straten, Per Thor

PY - 2019

Y1 - 2019

N2 - The TAM family of receptor tyrosine kinases (TYRO3, AXL, and MERTK) is known to be expressed on antigen-presenting cells and function as oncogenic drivers and as inhibitors of inflammatory responses. Both human and mouse CD8 T cells are thought to be negative for TAM receptor expression. In this study, we show that T-cell receptor (TCR)-activated human primary CD8 T cells expressed MERTK and the ligand PROS1 from day 2 postactivation. PROS1-mediated MERTK signaling served as a late costimulatory signal, increasing proliferation and secretion of effector and memory- associated cytokines. Knockdown and inhibition studies confirmed that this costimulatory effect was mediated through MERTK. Transcriptomic and metabolic analyses of PROS1-blocked CD8 T cells demonstrated a role of the PROS1-MERTK axis in differentiation of memory CD8 T cells. Finally, using tumor-infiltrating lymphocytes (TIL) from melanoma patients, we show that MERTK signaling on T cells improved TIL expansion and TIL-mediated autologous cancer cell killing. We conclude that MERTK serves as a late costimulatory signal for CD8 T cells. Identification of this costimulatory function of MERTK on human CD8 T cells suggests caution in the development of MERTK inhibitors for hematologic or solid cancer treatment.

AB - The TAM family of receptor tyrosine kinases (TYRO3, AXL, and MERTK) is known to be expressed on antigen-presenting cells and function as oncogenic drivers and as inhibitors of inflammatory responses. Both human and mouse CD8 T cells are thought to be negative for TAM receptor expression. In this study, we show that T-cell receptor (TCR)-activated human primary CD8 T cells expressed MERTK and the ligand PROS1 from day 2 postactivation. PROS1-mediated MERTK signaling served as a late costimulatory signal, increasing proliferation and secretion of effector and memory- associated cytokines. Knockdown and inhibition studies confirmed that this costimulatory effect was mediated through MERTK. Transcriptomic and metabolic analyses of PROS1-blocked CD8 T cells demonstrated a role of the PROS1-MERTK axis in differentiation of memory CD8 T cells. Finally, using tumor-infiltrating lymphocytes (TIL) from melanoma patients, we show that MERTK signaling on T cells improved TIL expansion and TIL-mediated autologous cancer cell killing. We conclude that MERTK serves as a late costimulatory signal for CD8 T cells. Identification of this costimulatory function of MERTK on human CD8 T cells suggests caution in the development of MERTK inhibitors for hematologic or solid cancer treatment.

U2 - 10.1158/2326-6066.CIR-18-0841

DO - 10.1158/2326-6066.CIR-18-0841

M3 - Journal article

C2 - 31266785

AN - SCOPUS:85071784139

VL - 7

SP - 1472

EP - 1484

JO - Cancer Immunology Research

JF - Cancer Immunology Research

SN - 2326-6066

IS - 9

ER -

ID: 227470415