Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy
Sara De Biasi1, Lara Gibellini2, Domenico Lo Tartaro2
1Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy. debiasisara@yahoo.it.
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.
Insights
Mucosal-associated invariant T (MAIT) cells are key biomarkers for predicting response to anti-PD-1 therapy in metastatic melanoma patients. Higher MAIT cell proportions indicate better treatment outcomes.
Area of Science:
- Immunology
- Oncology
- Cellular Biology
Background:
- Metastatic melanoma treatment relies on immune checkpoint inhibitors like anti-PD-1 therapy.
- Patient response to anti-PD-1 therapy is highly variable, necessitating predictive biomarkers.
- Identifying patients likely to benefit from immunotherapy is crucial for effective melanoma management.
Purpose of the Study:
- To investigate the role of circulating CD8+ T cells, including mucosal-associated invariant T (MAIT) cells, as biomarkers for anti-PD-1 therapy response in metastatic melanoma.
- To correlate immune cell profiles with treatment outcomes over a 6-month period.
Main Methods:
- Combined single-cell RNA-sequencing and multiparameter flow cytometry.
- Analyzed peripheral blood CD8+ T cells from 28 metastatic melanoma patients undergoing anti-PD-1 therapy.
- Monitored immune cell changes over 6 months, comparing responders (17) and non-responders (11).
Main Results:
- Responders exhibited significantly higher proportions of activated/proliferating CD8+ T cells and MAIT cells before and during therapy.
- MAIT cells in responders showed increased CXCR4 expression and granzyme B production.
- In silico analysis suggested MAIT cell infiltration into the tumor microenvironment.
- A threshold of >1.7% MAIT cells within the peripheral CD8+ T cell population predicted better treatment response.
Conclusions:
- MAIT cells represent a promising predictive biomarker for anti-PD-1 therapy efficacy in metastatic melanoma.
- Circulating MAIT cell levels can help stratify patients for immunotherapy.
- Further research into MAIT cell function in the tumor microenvironment is warranted.
