Inhibition of SUMOylation Induces Adaptive Antitumor Immunity against Pancreatic Cancer through Multiple Effects on the Tumor Microenvironment.

ABSTRACT: Improvement of outcome in patients with pancreatic ductal adenocarcinoma (PDAC) requires exploration of novel therapeutic targets. Thus far, most studies of PDAC therapies, including those inhibiting small ubiquitin-like modifications (SUMOylation), have focused on PDAC epithelial cell biology, yet SUMOylation occurs in a variety of cell types. The mechanisms by which SUMOylation impacts PDAC in the context of its tumor microenvironment are poorly understood. We used clinically relevant orthotopic PDAC mouse models to investigate the effect of SUMOylation inhibition using a specific, clinical-stage compound, TAK-981. In contrast to its inhibition of PDAC cell proliferation in vitro, the survival benefit conferred by TAK-981 in vivo is dependent on the presence of T cells, suggesting that i

SUBMITTER: Erdem S 

PROVIDER: S-EPMC11534524 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature