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Circulating CD8+ MAIT cells correlate with improved outcomes in anti-PD1 treated melanoma patients.

Vorwald, V. M.; Davis, D. M.; Van Gulick, R. J.; Torphy, R. J.; Borgers, J. S. W.; Klarquist, J.; Couts, K. L.; Amato, C. M.; Cogswell, D. T.; Fujita, M.; Davis, T.; Lozupone, C.; Medina, T. M.; Robinson, W. A.; Gapin, L. P.; McCarter, M. D.; Tobin, R. P.

2020-08-23 oncology
10.1101/2020.08.20.20178988
Show abstract

While much of the research concerning factors associated with responses to immunotherapies focuses on the contributions of conventional peptide-specific T cells, the role of unconventional T cells, such as mucosalassociated invariant T (MAIT) cells, in human melanoma remains largely unknown. MAIT cells are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting vitamin metabolites derived from bacteria. In this prospective clinical study, we sought to characterize MAIT cells in melanoma patients and determine their association with clinical outcomes. We identified tumor-infiltrating MAIT cells in melanomas across metastatic sites and found that the number of circulating MAIT cells is reduced in melanoma patients. However, circulating MAIT cell frequency is restored by anti-PD1 treatment in responding patients, correlating with treatment responses in which patients with high frequencies of MAIT cells exhibited improved overall survival. These data provide evidence for leveraging MAIT cells and their functions as novel targets for future therapies.

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