Regulatory mucosa-associated invariant T cells controlled by ß1 adrenergic receptor signaling contribute to hepatocellular carcinoma progression.
Hepatology
; 78(1): 72-87, 2023 07 01.
Article
em En
| MEDLINE
| ID: mdl-36626624
ABSTRACT
BACKGROUND AND AIMS:
The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver and have been linked to human HCC. However, their contributions to the progression of HCC are controversial due to the heterogeneity of MAIT cells, and new MAIT cell subsets remain to be explored. APPROACH ANDRESULTS:
Combining single cell RNA sequencing (scRNA-seq) and flow cytometry analysis, we performed phenotypic and functional studies and found that FOXP3 + CXCR3 + MAIT cells in HCC patients were regulatory MAIT cells (MAITregs) with high immunosuppressive potential. These MAITregs were induced under Treg-inducing condition and predominantly from FOXP3 - CXCR3 + MAIT cells, which displayed mild Treg-related features and represented a pre-MAITreg reservoir. In addition, the induction and function of MAITregs were promoted by ß1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively. In HCC patients, high proportion of the intratumoral MAITregs inhibited antitumor immune responses and was associated with poor clinical outcomes.CONCLUSIONS:
Together, we reveal an immunosuppressive subset of MAIT cells in HCC patients that contributes to HCC progression, and propose a control through neuroimmune crosstalk.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Células T Invariantes Associadas à Mucosa
/
Neoplasias Hepáticas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Hepatology
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China