The role of UTX in mediating sex differences during the CD8+ T cell antitumor response 3960

Description CD8+ T cells play a crucial role in the clearance of virally infected and transformed cells. There has been increasing evidence that a sex difference exists in the antitumor response with females having lower incidence and mortality rates for various non-reproductive tissue cancers. Many sex differences in immunity arise from two key areas, sex hormones and sex chromosomes. Sex hormones have been shown to impact antitumor immunity with higher levels of androgens in males leading to an exhausted, less cytotoxic CD8+ T cell. It is currently not well understood the role sex chromosomes play in antitumor immunity, however, it is thought that genes that escape X chromosome inactivation (XCI) may play a role. Previous literature has shown that the XCI escapee and epigenetic regulator UTX impacts sex differences in NK cells, however, how UTX impacts CD8+ T cell antitumor response is not yet known. Our preliminary data demonstrates that sex differences persist in MC38 tumor challenged gonadectomized mice. We also demonstrate that a T cell-specific deficiency of UTX (UTXTCD) leads to decreased survival and IFN-γ response against the MC38 cell line. Taken together, this data may elucidate the role UTX plays in CD8+ T cells during the antitumor response and how this contributes to sex differences. Funding Sources Supported by UCLA Eugene V.