Figure 1.

CTLs regulate tumor growth via cytostatic effects rather than cytotoxicity. B16 melanoma cells expressing a fluorescent ubiquitination-based cell cycle indicator (B16-fucci) fluoresce green in the S, G2, and M phases of the cell cycle, red in the G1 phase and yellow during the G1/S transition. Cytotoxic T lymphocytes (CTLs) infiltrate the tumor, where they recognize and directly kill a portion of the cancer cells. At the same time, interferon γ (IFNγ) secreted by CTLs induces wide spread G1 cell cycle arrest of additional tumor cells through the IFNγ receptor, phosphorylation of Stat1, downregulation of Skp2 and accumulation of its target p27 cyclin-dependent kinase inhibitor. The inhibition of tumor growth mediated by tumor-reactive CTLs is thus largely dependent on IFNγ-mediated cell cycle arrest rather than the cytolytic killing of tumor cells.