Co-treatment of ticagrelor and anti-PD-1 immunotherapy in tumor-associated macrophages reduces pancreatic cancer cell growth and migration through the TGF-β1/Smad2 pathway.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the third primary cause of cancer-related mortality in the US. PDAC is associated with an immunosuppressive tumor microenvironment (TME) that restricts the effectiveness of immunotherapies. Immunosuppressive tumor-associated macrophages (TAMs), the most abundant cell type in TME, express immune checkpoint ligands, including programmed cell death protein 1 (PD-1) ligand 1 (PD-L1). Targeting PD-1/PD-L1 alone has no effect in PDAC, highlighting the need for combination approaches. P2Y₁₂, an ADP receptor, is expressed by macrophages, and P2Y₁₂ antagonists promote phagocytosis, in turn, is linked to anti-tumor activity. Here, we tested the combined blockade of PD-1/PD-L1 and P2Y₁₂ on TAMs in pancreatic cancer. For this

SUBMITTER: Kang Y 

PROVIDER: S-EPMC12915496 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature