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EMBO Rep. 2017 Sep;18(9):1545-1558. doi: 10.15252/embr.201744075. Epub 2017 Jul 27.

Identification of a novel population of highly cytotoxic c-Met-expressing CD8+ T lymphocytes.

Author information

1
Department of Pathology and Immunology, School of Medicine, University of Geneva, Geneva, Switzerland.
2
Division of Dermatology, University Hospital of Geneva, Geneva, Switzerland.
3
Amal Therapeutics, Geneva, Switzerland.
4
Centre of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
5
Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
6
Department of Pathology and Immunology, School of Medicine, University of Geneva, Geneva, Switzerland patrice.lalive@hcuge.ch.
7
Department of Neurosciences, Division of Neurology, University Hospital of Geneva, Geneva, Switzerland.

Abstract

CD8+ cytotoxic T lymphocytes (CTLs) are critical mediators of anti-tumor immunity, and controlling the mechanisms that govern CTL functions could be crucial for enhancing patient outcome. Previously, we reported that hepatocyte growth factor (HGF) limits effective murine CTL responses via antigen-presenting cells. Here, we show that a fraction of murine effector CTLs expresses the HGF receptor c-Met (c-Met+ CTLs). Phenotypic and functional analysis of c-Met+ CTLs reveals that they display enhanced cytolytic capacities compared to their c-Met- CTL counterparts. Furthermore, HGF directly restrains the cytolytic function of c-Met+ CTLs in cell-mediated cytotoxicity reactions in vitro and in vivo and abrogates T-cell responses against metastatic melanoma in vivo Finally, we establish in three murine tumor settings and in human melanoma tissues that c-Met+ CTLs are a naturally occurring CD8+ T-cell population. Together, our findings suggest that the HGF/c-Met pathway could be exploited to control CD8+ T-cell-mediated anti-tumor immunity.

KEYWORDS:

CTL ; HGF ; cancer; c‐Met; tumor immunity

PMID:
28751311
PMCID:
PMC5579394
DOI:
10.15252/embr.201744075
[Indexed for MEDLINE]
Free PMC Article

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