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

Sara Biasi (), Lara Gibellini, Domenico Lo Tartaro, Simone Puccio, Claudio Rabacchi, Emilia M. C. Mazza, Jolanda Brummelman, Brandon Williams, Kelly Kaihara, Mattia Forcato, Silvio Bicciato, Marcello Pinti, Roberta Depenni, Roberto Sabbatini, Caterina Longo, Massimo Dominici, Giovanni Pellacani, Enrico Lugli and Andrea Cossarizza
Additional contact information
Sara Biasi: University of Modena and Reggio Emilia
Lara Gibellini: University of Modena and Reggio Emilia
Domenico Lo Tartaro: University of Modena and Reggio Emilia
Simone Puccio: Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital
Claudio Rabacchi: University of Modena and Reggio Emilia
Emilia M. C. Mazza: Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital
Jolanda Brummelman: Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital
Brandon Williams: Bio-Rad Laboratories
Kelly Kaihara: Bio-Rad Laboratories
Mattia Forcato: University of Modena and Reggio Emilia
Silvio Bicciato: University of Modena and Reggio Emilia
Marcello Pinti: University of Modena and Reggio Emilia
Roberta Depenni: University of Modena & Reggio Emilia
Roberto Sabbatini: University of Modena & Reggio Emilia
Caterina Longo: University of Modena and Reggio Emilia
Massimo Dominici: University of Modena and Reggio Emilia
Giovanni Pellacani: University of Modena and Reggio Emilia
Enrico Lugli: Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital
Andrea Cossarizza: University of Modena and Reggio Emilia

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21928-4

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