Tumor-derived exosomal tsRNA 3'tiRNA-AlaCGC in promoting fibroblast senescence and Galectin-9 secretion to induce immune tolerance in lung adenocarcinoma.

ABSTRACT: Given the heterogeneity of the tumor microenvironment (TME), neoadjuvant immunotherapy combined with chemotherapy benefits only a subset of lung adenocarcinoma (LUAD) patients, and the mechanisms of resistance remain unclear. Transfer RNA-derived small RNAs (tsRNAs) are a new class of non-coding RNAs that participate in the remodeling of the TME. Using high-throughput small RNA microarray analysis, we found elevated expression of tsRNA 3'tiRNA-AlaCGC in tumors of LUAD patients resistant to neoadjuvant therapy, and negatively correlated with the poor prognosis in LUAD patients. Furthermore, we discovered that tumor-derived exosome carrying 3'tiRNA-AlaCGC target fibroblasts to induce a senescence-associated secretory phenotype (SASP) by inhibiting FOXO3, and activating the TGF-β/Smad3 pathwa

SUBMITTER: Zhao G 

PROVIDER: S-EPMC12379295 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature