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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; Carnaz Simões, Ana Micaela; Martinenaite, Evelina; Halldórsdóttir, Hólmfridur R; Andersen, Mads Hald; Olofsson, Gitte Holmen; Svane, Inge Marie; Rasmussen, Lene Juel; Met, Özcan; Becker, Jürgen C; Donia, Marco; Desler, Claus; Thor Straten, Per.
Afiliación
  • Peeters MJW; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark. per.thor.straten@regionh.dk marlies.peeters@regionh.dk.
  • Dulkeviciute D; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Draghi A; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Ritter C; Translational Skin Cancer Research, University Hospital Essen, German Cancer Consortium (DKTK) Partner Site Essen and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Rahbech A; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Skadborg SK; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Seremet T; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Carnaz Simões AM; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Martinenaite E; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Halldórsdóttir HR; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Andersen MH; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Olofsson GH; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Svane IM; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Rasmussen LJ; Department of Oncology, University Hospital Herlev, Copenhagen, Denmark.
  • Met Ö; Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Denmark.
  • Becker JC; Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark.
  • Donia M; Department of Oncology, University Hospital Herlev, Copenhagen, Denmark.
  • Desler C; Department of Immunology and Microbiology, Inflammation and Cancer Group, University of Copenhagen, Copenhagen, Denmark.
  • Thor Straten P; Translational Skin Cancer Research, University Hospital Essen, German Cancer Consortium (DKTK) Partner Site Essen and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Cancer Immunol Res ; 7(9): 1472-1484, 2019 Sep.
Article en En | MEDLINE | ID: mdl-31266785
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Tirosina Quinasa c-Mer Límite: Humans Idioma: En Revista: Cancer Immunol Res Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Tirosina Quinasa c-Mer Límite: Humans Idioma: En Revista: Cancer Immunol Res Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos