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Cell. 2016 Sep 8;166(6):1485-1499.e15. doi: 10.1016/j.cell.2016.07.046. Epub 2016 Aug 25.

γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation.

Author information

1
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.
2
S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
3
Department of Biochemistry, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
4
Department of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA.
5
Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington Oxford OX3 7FY, UK.
6
Department of Biochemistry, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
7
Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
8
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. Electronic address: george.miller@nyumc.org.

Abstract

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.

KEYWORDS:

Kras; cancer; checkpoint ligands

Comment in

PMID:
27569912
PMCID:
PMC5017923
DOI:
10.1016/j.cell.2016.07.046
[Indexed for MEDLINE]
Free PMC Article

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