Elevated Mast Cell Abundance Is Associated with Enrichment of CCR2+ Cytotoxic T Cells and Favorable Prognosis in Lung Adenocarcinoma.
Cancer Res
; 83(16): 2690-2703, 2023 08 15.
Article
em En
| MEDLINE
| ID: mdl-37249584
ABSTRACT
Mast cells constitute indispensable immunoregulatory sentinel cells in the tumor microenvironment. A better understanding of the regulation and functions of mast cells in lung adenocarcinoma (LUAD) could uncover therapeutic approaches to reprogram the immunosuppressive tumor microenvironment. Here, we performed flow cytometry and single-cell RNA sequencing (scRNA-seq) of patient LUAD samples to comprehensively characterize LUAD-infiltrating mast cells. Mast cells exhibited functional heterogeneity and were enriched in LUAD with ground-glass opacity features (gLUAD). The mast cells in gLUAD exhibited proinflammatory and chemotactic properties while those in radiologically solid LUAD (sLUAD) were associated with tumor angiogenesis. Mast cells were an important source of CCL2 and correlated with the recruitment of CCR2+ CTL, a specific subcluster of preexhausted T cells with tissue-resident memory phenotype and enhanced cytotoxicity. Increased infiltration of mast cells and CCR2+ CTLs and their colocalization showed a strong association with favorable prognosis after surgery but were not associated with improved survival after chemotherapy. Collectively, these findings reveal a key role of mast cells in LUAD and their potential cross-talk with CTLs, suggesting that targeting mast cells may be an immunotherapeutic strategy for LUAD. SIGNIFICANCE:
Comprehensive characterization of mast cells in lung adenocarcinoma elucidates their heterogeneity and identifies interplay between mast cells and CCR2+ T cells that is associated with a favorable prognosis.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Pulmao
Base de dados:
MEDLINE
Assunto principal:
Adenocarcinoma de Pulmão
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China