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

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 mucosal-associated 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.

Thymus-derived hormonal and cellular control of cancer

“…Due to their multiple functions often associated with successful anti-tumor immune responses, MAIT cells represent an attractive population to explore for their potential roles in anti-tumor immunity (96). However, these cells represent a controversial topic in the field of tumor immunology with studies showing conflicting results regarding as to whether they contribute to tumor growth, tumor regression, or play a neutral role in human cancers (97,98). Once activated, tumor-infiltrating MAIT cells display decreased IFN-g and TNF-a and increase IL-17 production.…”

T‐cell subsets in the skin and their role in inflammatory skin disorders

“…In metastatic melanoma patients treated with anti-PD-1 therapy, an increase in CD8 + T cells and MAIT cells was demonstrated specifically in responders. As patients with >1.7% of MAIT cells among the peripheral CD8 + T-cell population showed a better response to treatment, MAIT cells may be considered a biomarker for melanoma patients responding to anti-PD-1 therapy 155,156 (Table 2).…”