Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

MERTK Acts as a Costimulatory Receptor on Human CD8+ T Cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma-Implications for Adoptive Cell Therapy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Cutaneous adverse reactions to anti-PD-1 treatment - a systematic review

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. In vitro 4-1BB stimulation promotes expansion of CD8+ tumor-infiltrating lymphocytes from various sarcoma subtypes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftCancer immunology research
ISSN2326-6066
DOI
StatusUdgivet - sep. 2019

Bibliografisk note

©2019 American Association for Cancer Research.

ID: 57728694