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Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-21928-4

2041-1723

Sara De Biasi, Lara Gibellini, Domenico Lo Tartaro, Simone Puccio, Claudio Rabacchi, Emilia Maria Cristina Mazza, Jolanda Brummelman, Brandon Williams, Kelly A. Kaihara, Mattia Forcato, Silvio Bicciato, Marcello Pinti, Roberta Depenni, Roberto Sabbatini, Caterina Longo, Massimo Dominici, Giovanni Pellacani, Enrico Lugli, Andrea Cossarizza,

Cancer Immunotherapy and Biomarkers

Abstract Immune checkpoint inhibitors are used for treating patients with metastatic melanoma. Since the response to treatment is variable, biomarkers are urgently needed to identify patients who may benefit from such therapy. Here, we combine single-cell RNA-sequencing and multiparameter flow cytometry to assess changes in circulating CD8 + T cells in 28 patients with metastatic melanoma starting anti-PD-1 therapy, followed for 6 months: 17 responded to therapy, whilst 11 did not. Proportions of activated and proliferating CD8 + T cells and of mucosal-associated invariant T (MAIT) cells are significantly higher in responders, prior to and throughout therapy duration. MAIT cells from responders express higher level of CXCR4 and produce more granzyme B. In silico analysis support MAIT presence in the tumor microenvironment. Finally, patients with >1.7% of MAIT among peripheral CD8 + population show a better response to treatment. Our results thus suggest that MAIT cells may be considered a biomarker for patients responding to anti-PD-1 therapy.