DNA hypo-methylation and expression of GBP4 induces T cell exhaustion in pancreatic cancer.

ABSTRACT: Immunotherapy for pancreatic ductal carcinoma (PDAC) remains disappointing due to the repressive tumor microenvironment and T cell exhaustion, in which the roles of interferon-stimulated genes were largely unknown. Here, we focused on a typical interferon-stimulated gene, GBP4, and investigated its potential diagnostic and therapeutic value in pancreatic cancer. Expression analysis on both local samples and public databases indicated that GBP4 was one of the most dominant GBP family members present in the PDAC microenvironment, and the expression level of GBP4 was negatively associated with patient survival. We then identified DNA hypo-methylation in regulatory regions of GBP4 in PDAC, and validated its regulatory role on GBP4 expression via performing targeted methylation using dCas9-SunT

SUBMITTER: Tasiheng Y 

PROVIDER: S-EPMC11306721 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature