Identification of a novel population of highly cytotoxic c‐Met‐expressing CD8+ T lymphocytes. (27th July 2017)

• Record Type: Journal Article
• Authors: Benkhoucha, Mahdia; Molnarfi, Nicolas; Kaya, Gürkan; Belnoue, Elodie; Bjarnadóttir, Kristbjörg; Dietrich, Pierre‐Yves; Walker, Paul R; Martinvalet, Denis; Derouazi, Madiha; Lalive, Patrice H
• Is Part Of: EMBO reports. Volume 18:Number 9(2017)
• Page Start: 1545
• Page End: 1558
• Publication Date: 2017-07-27
• Subjects: cancer -- c‐Met -- CTL -- HGF -- tumor immunity; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201744075
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: Cytotoxic T lymphocytes (CTLs) play a critical role in cancer immunity. A fraction of murine effector CTLs expresses the HGF receptor c‐Met, and the HGF/c‐MET signaling pathway has a specific role in modulating CTL responses. Expression of c‐Met identifies a subset of highly cytotoxic CD8 + T lymphocytes (CTLs). CTLs expressing c‐Met are found within tumors. Hepatocyte growth factor (HGF) restrains the cytotoxic activities of c‐Met + CTLs. Abstract : Cytotoxic T lymphocytes (CTLs) play a critical role in cancer immunity. A fraction of murine effector CTLs expresses the HGF receptor c‐Met, and the HGF/c‐MET signaling pathway has a specific role in modulating CTL responses.