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CXCR6-positive circulating mucosal-associated invariant T cells can identify patients with non-small cell lung cancer responding to anti-PD-1 immunotherapy.
- Source :
-
Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2024 May 03; Vol. 43 (1), pp. 134. Date of Electronic Publication: 2024 May 03. - Publication Year :
- 2024
-
Abstract
- Background: Mucosal-associated invariant T (MAIT) cells have been reported to regulate tumor immunity. However, the immune characteristics of MAIT cells in non-small cell lung cancer (NSCLC) and their correlation with the treatment efficacy of immune checkpoint inhibitors (ICIs) remain unclear.<br />Patients and Methods: In this study, we performed single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence assays to determine the proportion and characteristics of CD8+MAIT cells in patients with metastatic NSCLC who did and did not respond to anti-PD-1 therapy. Survival analyses were employed to determine the effects of MAIT proportion and C-X-C chemokine receptor 6 (CXCR6) expression on the prognosis of patients with advanced NSCLC.<br />Results: The proportion of activated and proliferating CD8+MAIT cells were significantly higher in responders-derived peripheral blood mononuclear cells (PBMCs) and lung tissues before anti-PD-1 therapy, with enhanced expression of cytotoxicity-related genes including CCL4, KLRG1, PRF1, NCR3, NKG7, GZMB, and KLRK1. The responders' peripheral and tumor-infiltrating CD8+MAIT cells showed an upregulated CXCR6 expression. Similarly, CXCR6+CD8+MAIT cells from responders showed higher expression of cytotoxicity-related genes, such as CST7, GNLY, KLRG1, NKG7, and PRF1. Patients with ≥15.1% CD8+MAIT cells to CD8+T cells ratio and ≥35.9% CXCR6+CD8+MAIT cells to CD8+MAIT cells ratio in peripheral blood showed better progression-free survival (PFS) after immunotherapy. The role of CD8+MAIT cells in lung cancer immunotherapy was potentially mediated by classical/non-classical monocytes through the CXCL16-CXCR6 axis.<br />Conclusion: CD8+MAIT cells are a potential predictive biomarker for patients with NSCLC responding to anti-PD-1 therapy. The correlation between CD8+MAIT cells and immunotherapy sensitivity may be ascribed to high CXCR6 expression.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Male
Female
Middle Aged
Aged
Prognosis
Programmed Cell Death 1 Receptor antagonists & inhibitors
Programmed Cell Death 1 Receptor metabolism
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung immunology
Carcinoma, Non-Small-Cell Lung pathology
Receptors, CXCR6 metabolism
Lung Neoplasms drug therapy
Lung Neoplasms immunology
Lung Neoplasms pathology
Lung Neoplasms metabolism
Lung Neoplasms genetics
Mucosal-Associated Invariant T Cells immunology
Mucosal-Associated Invariant T Cells metabolism
Immunotherapy methods
Immune Checkpoint Inhibitors therapeutic use
Immune Checkpoint Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1756-9966
- Volume :
- 43
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of experimental & clinical cancer research : CR
- Publication Type :
- Academic Journal
- Accession number :
- 38698468
- Full Text :
- https://doi.org/10.1186/s13046-024-03046-3