| First Author | Clever D | Year | 2016 |
| Journal | Cell | Volume | 166 |
| Issue | 5 | Pages | 1117-1131.e14 |
| PubMed ID | 27565342 | Mgi Jnum | J:234541 |
| Mgi Id | MGI:5790206 | Doi | 10.1016/j.cell.2016.07.032 |
| Citation | Clever D, et al. (2016) Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche. Cell 166(5):1117-1131.e14 |
| abstractText | Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T-cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4(+)-regulatory T (Treg) cell induction, and restrain CD8(+) T cell effector function. Tumor colonization is accompanied by PHD-protein-dependent induction of pulmonary Treg cells and suppression of IFN-gamma-dependent tumor clearance. T-cell-intrinsic deletion or pharmacological inhibition of PHD proteins limits tumor colonization of the lung and improves the efficacy of adoptive cell transfer immunotherapy. Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis. PAPERCLIP. |
