The proposed research aims to elucidate the role of XCI in T cells within the tumor microenvironment and its implications for cancer immunotherapy. I expect to identify sex-specific biomarkers through scRNA-seq analysis, uncovering gene expression profiles and XCI escapee genes that predict treatment outcomes. In vitro studies will characterize how XCI patterns affect T cell function, revealing key genes that influence immune responses. Using CRISPR-based modulation, I aim to discover novel therapeutic targets that enhance T cell efficacy. Additionally, I will evaluate synergistic effects of combining XCI-modulated T cells with immune checkpoint inhibitors, potentially leading to more effective combination therapies. This project represents a pioneering effort to dissect the role of XCI in T cell responses and its implications for cancer immunotherapy. These findings will not only fill a critical knowledge gap but also have significant clinical implications for the development of sex-specific treatments in oncology.