Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy.
J Immunother Cancer
; 11(1)2023 01.
Article
en En
| MEDLINE
| ID: mdl-36657812
ABSTRACT
BACKGROUND:
Immune-checkpoint inhibitors (ICIs) remain ineffective in a large group of non-small cell lung cancer (NSCLC) patients. Mucosal-associated invariant T (MAIT) cells, a population of unconventional innate-like T lymphocytes abundant in the human body, play important roles in human malignancies. Little is known about the immune characteristics of MAIT cells in NSCLC and correlation with prognosis and response rate of ICIs treatment.METHODS:
To investigate the distribution, activation status, and function of MAIT cells in NSCLC patients and their correlations with anti-PD-1 immunotherapy, MAIT cells in peripheral blood, tumor and paratumor samples from NSCLC patients with or without anti-PD-1 immunotherapy were analyzed using flow cytometry and single-cell RNA-sequencing.RESULTS:
MAIT cells were enriched in the tumor lesions of NSCLC patients migrating from peripheral blood via the CCR6-CCL20 axis. Both peripheral and tumor-infiltrating MAIT cells displayed an exhausted phenotype with upregulated PD-1, TIM-3, and IL-17A while less IFN-γ. Anti-PD-1 therapy reversed the function of circulating MAIT cells with higher expression of IFN-γ and granzyme B. Subcluster MAIT-17s (defined as cells highly expressing exhausted and Th17-related genes) mainly infiltrated in the non-responsive tissues, while the subcluster MAIT-IFNGRs (cells expressing genes related to cytotoxic function) were mainly enriched in responsive tissues. Moreover, we found predictive value of circulating MAIT cells for anti-PD-1 immunotherapy in NSCLC patients.CONCLUSIONS:
MAIT cells shifted to an exhausted tumor-promoting phenotype in NSCLC patients and the circulating MAIT subset could be a predictor for patients who respond to anti-PD-1 immunotherapy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
/
Células T Invariantes Asociadas a Mucosa
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Immunother Cancer
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
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UNITED KINGDOM