OX40 engagement promotes potent tumoricidial CD4+ T cells (P2199)

Abstract

Abstract Several immune-based strategies are currently used to treat melanoma in the clinic; however, very few result in a complete response. CD4+ T cells are potent mediators of anti-tumor immunity and adoptive transfer of specific CD4+ T cells leads to tumor regression. OX40, a costimulatory molecule expressed primarily on activated CD4+ T cells, promotes and enhances anti-tumor immunity with limited success on large tumors in mice. Here we show that OX40 engagement induces a novel CD4+ T cell population characterized by the expression of the master regulator eomesodermin that leads to both terminal differentiation and central memory phenotype, with concomitant secretion of Th1 and Th2 cytokines. This subpopulation of CD4+ T cells eradicates very advanced melanomas in mice, and an analogous population of human tumor-specific CD4+ T cells can kill melanoma in an in vitro system. Interestingly, the combination therapy effectively eliminates tumor escape variants. Our results show that these uniquely programmed effector CD4+ T cells have a distinctive phenotype with increased tumoricidal capability and support the use of immune modulation in reprogramming the phenotype of CD4+ T cells