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 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. [ABSTRACT FROM AUTHOR]