Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αβT cells. Although αβT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4+ and CD8+ T cell infiltration and immunogenicity and induced tumor protection suggesting that γδT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe γδT cells as central regulators of effector T cell activation in cancer via novel cross-talk.
|State||Published - Sep 8 2016|
Bibliographical noteFunding Information:
This work was supported by grants for the German Research Foundation (L.S.), the National Pancreas Foundation (C.P.Z.), the Pancreatic Cancer Action Network (G.M.), the Lustgarten Foundation (G.M.), and National Institute of Health Awards CA155649 (G.M.), CA168611 (G.M.), and CA193111 (G.M. and A.T.-H.). We thank the New York University Langone Medical Center (NYU LMC) Histopathology Core Facility, the NYU LMC Flow Cytometry Core Facility, the NYU LMC Microscopy Core Facility, and the NYU LMC BioRepository Center, each supported in part by the Cancer Center Support Grant P30CA016087 and by grant UL1 TR000038 from the National Center for the Advancement of Translational Science (NCATS).
© 2016 Elsevier Inc.
- checkpoint ligands
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)