Tissue factor promotes TREX1 protein stability to evade cGAS-STING innate immune response in pancreatic ductal adenocarcinoma.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) remains the most challenging human malignancy that urgently needs effective therapy. Tissue factor (TF) is expressed in ~80% of PDAC and represents a potential therapeutic target. While a novel TF-ADC (MRG004A) demonstrated efficacy for PDAC and TNBC in a Phase I/II trial [Ref. 18], the functional role of TF in PDAC remains incompletely understood. We investigated the relationship between TF and the innate STING pathway. We found that patients with TF-overexpression had poor survival, very low levels of P-STING/P-TBK1, reduced amounts of ISGs and chemokines as well as low numbers of cytotoxic immunocytes in their tumor. In experimental models of mouse and human PDAC, tumor cell-intrinsic TF expression played a major role in silencing the cytosolic mi

SUBMITTER: Xue Y 

PROVIDER: S-EPMC11888988 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature