AbstractWhile the beneficial role played by tissue-resident memory T cells (Trm) in tumor control has emerged, the chemotactic mechanisms associated with their localization and retention in the tumor microenvironment (TME) of cancers including ovarian are poorly understood. The current study has identified chemokine receptor CXCR6 as crucial for Trm responses to ovarian cancer by promoting their localization and retention in the ovarian tumor microenvironment. In human ovarian cancer patients, CXCR6 significantly marked CD8+ CD103+ tumor-infiltrating Trm cells. Functional studies in mice revealed high expression of CXCR6 in tumor-specific T cells that reside in tissues, but not by those in circulation. Knockout of CXCR6 in tumor-specific T cells led to a heightened circulatory response in blood, but diminished resident memory cell accumulation in tumors, culminating in poor tumor control. Analysis of Wild type (Wt.) and CXCR6KO (KO) tumor-specific T cells trafficking in recipient mice using bioluminescent imaging revealed that compared to Wt., KO T cells preferentially localized to the spleen, indicating the possibility of reduced retention in tumor tissues. These findings indicate that CXCR6 by mediating increased retention of tumor-specific T cells in the ovarian tumor microenvironment, promotes resident memory T cell-mediated surveillance and control of ovarian cancer.
CXCR6 governs the retention of tissue-resident memory T cells to promote enhanced surveillance and control of ovarian cancer