Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy
| Autor: | Biasi, S. De, Gibellini, L., Tartaro, D. Lo, Puccio, S., Rabacchi, C., Mazza, E.M.C., Brummelman, J., Williams, B., Kaihara, K., Forcato, M., Bicciato, S., Pinti, M., Depenni, R., Sabbatini, R., Longo, C., Dominici, M., Pellacani, G., Lugli, E., Cossarizza, A. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Aged
80 and over Male Receptors CXCR4 Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Science Programmed Cell Death 1 Receptor T cells Translational immunology CD8-Positive T-Lymphocytes Middle Aged Antibodies Monoclonal Humanized Granzymes Mucosal-Associated Invariant T Cells Article Prognostic markers Humans Female Immunotherapy Biomarkers Aged |
| Zdroj: | Nature Communications, 12 Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) Nature Communications, 12, 1 |
| ISSN: | 2041-1723 |
| Popis: | 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. Immune checkpoint inhibition (ICI) shows potential for cancer therapies, but response rates vary. Here, the authors use single-cell analyses to show that, in a 28 patient cohort, patients stratified by mucosal-associated invariant T (MAIT) percentages show different response rates, and ICI responders have more MAIT cells expressing CXCR4 and granzyme B. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|