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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Daley, D; Zambirinis, CP; Seifert, L; Akkad, N; Mohan, N; Werba, G; Barilla, R; Torres-Hernandez, A; Hundeyin, M; Mani, VRK; Avanzi, A; Tippens, D; Narayanan, R; Jang, J-E; Newman, E; Pillarisetty, VG; Dustin, ML; Bar-Sagi, D; Hajdu, C; Miller, G

Published Date

  • September 2016

Published In

Volume / Issue

  • 166 / 6

Start / End Page

  • 1485 - 1499.e15

PubMed ID

  • 27569912

Pubmed Central ID

  • 27569912

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2016.07.046

Language

  • eng