BxPC-3-Derived Small Extracellular Vesicles Induce FOXP3+ Treg through ATM-AMPK-Sirtuins-Mediated FOXOs Nuclear Translocations.

ABSTRACT: Immunotherapy in pancreatic ductal adenocarcinoma (PDAC) treatment faces serious challenges, due particularly to the poor immunogenicity. Cancer cell-derived small extracellular vesicles (sEVs) play important roles in damaging the immune system. However, the effects of pancreatic cancer-derived sEVs on T lymphocytes are unknown. Here we investigated changes in phenotypes and signal transduction pathways in sEVs-treated T lymphocytes. We identified the overexpression of immune checkpoint proteins PD-1, PD-L1, CTLA4, and Tim-3 and the enrichment of FOXP3+ Treg cluster in sEVs-treated T lymphocytes by CyTOF. Gene set enrichment analysis revealed that DNA damage response and metabolic pathways might be involved in sEVs-induced Tregs. ATM, AMPK, SIRT1, SIRT2, and SIRT6 were activated sequential

SUBMITTER: Shen T 

PROVIDER: S-EPMC7452591 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature