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

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Published in EMBO reports. 2017, vol. 18, no. 9, p. 1545-1558
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.
PMID: 28751311
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Research groups Immunobiologie des tumeurs du cerveau (669)
Immunothérapie des cancers (42)
Scléroses en plaques, neuroimmunologie, encéphalite autoimmune expérimentale (843)
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BENKHOUCHA, Mahdia et al. Identification of a novel population of highly cytotoxic c-Met-expressing CD8(+) T lymphocytes. In: EMBO Reports, 2017, vol. 18, n° 9, p. 1545-1558. doi: 10.15252/embr.201744075 https://archive-ouverte.unige.ch/unige:97077

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Deposited on : 2017-09-27

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