CXCR6 governs the retention of tissue-resident memory T cells to promote enhanced surveillance and control of ovarian cancer

Muthuswamy, R.; McGray, A. R.; Battaglia, S.; He, W.; Miliotto, A.; Eppolito, C. A.; Litchy, B. D.; Shrikant, P.; Odunsi, K.

doi:10.1101/2020.12.02.401729

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bioRxiv · 10.1101/2020.12.02.401729

CXCR6 governs the retention of tissue-resident memory T cells to promote enhanced surveillance and control of ovarian cancer

Muthuswamy, R.·McGray, A. R.·Battaglia, S.·He, W.·Miliotto, A.·Eppolito, C. A.·Litchy, B. D.·Shrikant, P.·Odunsi, K.

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Abstract

PurposeResident memory CD8 T cells owing to their ability to reside and persist in peripheral tissues, impart adaptive sentinel activity and amplify local immune response, have beneficial implications for tumor surveillance and control. The current study aims to clarify the less known chemotactic mechanisms that govern the localization, retention, and residency of memory CD8 T cells in the ovarian tumor microenvironment. Experimental DesignRNA/FACS based profiling of chemokine receptor expression in CD8+ resident memory T cells in human ovarian cancer and analyze their association with survival. Analyze chemokine receptor role in anti-tumor response and control by resident memory T cells using prophylactic mice models of ovarian cancer, treated with adoptive transfer of OT1 T cells and vaccination with maraba virus-OVA to target Ovalbumin expressing tumor. ResultsChemokine receptor profiling of CD8+CD103+ resident memory TILs in ovarian cancer patients revealed high expression of CXCR6. Analysis of the TCGA ovarian cancer database revealed CXCR6 to be associated with CD103 and increased patient survival. Functional studies in mouse models of ovarian cancer revealed that CXCR6 is a marker of resident, but not circulatory tumor-specific memory CD8 T cells. Knockout of CXCR6 in tumor-specific CD8 T cells showed reduced retention in tumor tissues leading to diminished resident memory responses and poor control of ovarian cancer ConclusionsCXCR6 by promoting increased retention in tumor tissues serves a critical role in resident memory T cell-mediated immunosurveillance and control of ovarian cancer. Future studies warrant exploiting CXCR6 to promote resident memory response in cancers.

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Muthuswamy, R., McGray, A. R., Battaglia, S., He, W., Miliotto, A., Eppolito, C. A., Litchy, B. D., Shrikant, P., Odunsi, K.. 2020-12-02. CXCR6 governs the retention of tissue-resident memory T cells to promote enhanced surveillance and control of ovarian cancer. https://doi.org/10.1101/2020.12.02.401729

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