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Updated: Jan 22, 2026

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

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

Marlies J W Peeters1, Donata Dulkeviciute2, Arianna Draghi2

  • 1Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Copenhagen, Denmark. per.thor.straten@regionh.dk marlies.peeters@regionh.dk.

Cancer Immunology Research
|July 4, 2019
PubMed

Insights

Activated CD8+ T cells express MERTK, a receptor tyrosine kinase, which enhances their proliferation and cytokine secretion. This MERTK signaling also boosts tumor-infiltrating lymphocytes in melanoma, suggesting caution with MERTK inhibitors.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • TAM receptor tyrosine kinases (TYRO3, AXL, MERTK) are involved in immune regulation and cancer.
  • CD8+ T cells were previously thought to lack TAM receptor expression.

Purpose of the Study:

  • To investigate the expression and function of TAM receptors, specifically MERTK, in activated human CD8+ T cells.
  • To determine the role of MERTK signaling in T cell responses and anti-tumor immunity.

Main Methods:

  • T-cell receptor activation of primary human CD8+ T cells.
  • Analysis of MERTK and PROS1 expression post-activation.
  • Knockdown and inhibition studies to assess MERTK function.
  • Transcriptomic and metabolic analyses.
  • Studies using tumor-infiltrating lymphocytes (TIL) from melanoma patients.

Main Results:

  • TCR-activated human CD8+ T cells express MERTK and its ligand PROS1.
  • PROS1-mediated MERTK signaling acts as a late costimulatory signal, enhancing T cell proliferation and cytokine production.
  • MERTK signaling is crucial for memory CD8+ T cell differentiation.
  • MERTK signaling on T cells improves TIL expansion and cancer cell killing in melanoma.

Conclusions:

  • MERTK functions as a late costimulatory signal for human CD8+ T cells.
  • The PROS1-MERTK axis plays a significant role in T cell immunity and anti-tumor responses.
  • Targeting MERTK warrants caution due to its beneficial role in T cell function and anti-cancer immunity.

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