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

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 and and abrogates T-cell responses against metastatic melanoma 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.