Distinct response to IL-1β blockade in liver- and lung-specific metastasis mouse models of pancreatic cancer with heterogeneous tumor microenvironments.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a heterogeneous tumor microenvironment (TME). The mechanism by which this heterogeneity confers resistance against immunotherapy remains unclear. Interleukin- 1β (IL-1β) is a proinflammatory cytokine that regulates heterogeneous cancer associated fibroblast (CAF) phenotype and promotes an immunosuppressive TME. Anti-IL-1β monoclonal antibody significantly enhanced the anti-tumor activity of anti-PD-1 in a preclinical model of PDAC. However, clinical trials have shown limited activity of the anti-IL-1β and anti-PD-1 combination. Therefore, we hypothesize that anti-tumor immune response to the combination of anti-IL-1β and anti-PD-1 antibodies is context-dependent and would be affected by the TME heterogeneity in

SUBMITTER: Chen SY 

PROVIDER: S-EPMC11823153 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature