The Dual Role of the NFATc2/galectin-9 Axis in Modulating Tumor-Initiating Cell Phenotypes and Immune Suppression in Lung Adenocarcinoma.
Adv Sci (Weinh)
; 11(20): e2306059, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38528665
ABSTRACT
Tumor-initiating cells (TICs) resilience and an immunosuppressive microenvironment are aggressive oncogenic phenotypes that contribute to unsatisfactory long-term outcomes in lung adenocarcinoma (LUAD) patients. The molecular mechanisms mediating the interaction between TICs and immune tolerance have not been elucidated. The role of Galectin-9 in oncogenesis and immunosuppressive microenvironment is still unknown. This study explored the potential role of galectin-9 in TIC regulation and immune modulation in LUAD. The results show that galectin-9 supports TIC properties in LUAD. Co-culture of patient-derived organoids and matched peripheral blood mononuclear cells showed that tumor-secreted galectin-9 suppressed T cell cytotoxicity and induced regulatory T cells (Tregs). Clinically, galectin-9 is upregulated in human LUAD. High expression of galectin-9 predicted poor recurrence-free survival and correlated with high levels of Treg infiltration. LGALS9, the gene encoding galectin-9, is found to be transcriptionally regulated by the nuclear factor of activated T cells 2 (NFATc2), a previously reported TIC regulator, via in silico prediction and luciferase reporter assays. Overall, the results suggest that the NFATc2/galectin-9 axis plays a dual role in TIC regulation and immune suppression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
/
Galectinas
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Factores de Transcripción NFATC
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Adenocarcinoma del Pulmón
/
Neoplasias Pulmonares
Límite:
Humans
Idioma:
En
Revista:
Adv Sci (Weinh)
Año:
2024
Tipo del documento:
Article
País de afiliación:
China