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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.

Original publication

DOI

10.1016/j.cell.2016.07.046

Type

Journal article

Journal

Cell

Publication Date

09/2016

Volume

166

Pages

1485 - 1499.e15

Addresses

S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.

Keywords

T-Lymphocytes, Cells, Cultured, Epithelial Cells, Animals, Mice, Inbred C57BL, Humans, Mice, Carcinoma, Pancreatic Ductal, Chemokines, Ligands, Lymphocyte Activation, Signal Transduction, Female, Male, Adaptive Immunity, Tumor Microenvironment, Carcinogenesis