?? T Cells Support Pancreatic Oncogenesis by Restraining ?? T Cell Activation.

ABSTRACT: Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated ??T cell population, which constituted ?40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of ??T cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of ??T cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of ??T cells. Although ??T cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon ??T cell ablation. PDA-infiltrating ??T cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in ??T cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that ??T cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe ??T cells as central regulators of effector T cell activation in cancer via novel cross-talk.

SUBMITTER: Daley D 

PROVIDER: S-EPMC5017923 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature