Targeting tumor-intrinsic TAK1 triggers anti-tumor immunity and sensitizes pancreatic cancer to checkpoint blockade.

ABSTRACT:

Background and aims

Targeting the Transforming Growth Factor-β (TGF-β) pathway to reverse the immunologically "cold" tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful, warranting novel therapeutic strategies.

Methods

We developed a novel tumor-CD8 T cell co-culture to interrogate the TGF-β signaling pathways that promotes T cell-mediated cytotoxicity. We performed multiplex immunohistochemistry (mIHC) on human PDAC samples to correlate cell-type specific TGF-β pathway activation and CD8 T cell abundance. We employed specific pathway inhibitor and newly generated genetically-engineered mouse models (GEMMs) and confirmed our findings using single-cell RNA sequencing, flow cytometry and mIHC. We performed proteomics and vari

SUBMITTER: Bansod SP 

PROVIDER: S-EPMC12632323 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature