Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.

Methods

We used an unbiased screening approach of T cell resistant and sensitive murine KPC (Kras^LSL-G12D/+; Trp53^fl/fl; Ptf1a^Cre/+ ) PDAC cells in a three-dimensional co-culture platform with syngeneic antigen-educated T cells to id

SUBMITTER: Lahusen A 

PROVIDER: S-EPMC11748943 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature