| First Author | Daley D | Year | 2016 |
| Journal | Cell | Volume | 166 |
| Issue | 6 | Pages | 1485-1499.e15 |
| PubMed ID | 27569912 | Mgi Jnum | J:236387 |
| Mgi Id | MGI:5805998 | Doi | 10.1016/j.cell.2016.07.046 |
| Citation | Daley D, et al. (2016) gammadelta T Cells Support Pancreatic Oncogenesis by Restraining alphabeta T Cell Activation. Cell 166(6):1485-1499.e15 |
| abstractText | Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated gammadeltaT cell population, which constituted approximately 40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of gammadeltaT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of gammadeltaT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of alphabetaT cells. Although alphabetaT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon gammadeltaT cell ablation. PDA-infiltrating gammadeltaT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in gammadeltaT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that gammadeltaT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe gammadeltaT cells as central regulators of effector T cell activation in cancer via novel cross-talk. |
