| First Author | Park JH | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 3 | Pages | 336-346 |
| PubMed ID | 33574616 | Mgi Jnum | J:306038 |
| Mgi Id | MGI:6706736 | Doi | 10.1038/s41590-020-00860-7 |
| Citation | Park JH, et al. (2021) Tumor hypoxia represses gammadelta T cell-mediated antitumor immunity against brain tumors. Nat Immunol 22(3):336-346 |
| abstractText | The anatomic location and immunologic characteristics of brain tumors result in strong lymphocyte suppression. Consequently, conventional immunotherapies targeting CD8 T cells are ineffective against brain tumors. Tumor cells escape immunosurveillance by various mechanisms and tumor cell metabolism can affect the metabolic states and functions of tumor-infiltrating lymphocytes. Here, we discovered that brain tumor cells had a particularly high demand for oxygen, which affected gammadelta T cell-mediated antitumor immune responses but not those of conventional T cells. Specifically, tumor hypoxia activated the gammadelta T cell protein kinase A pathway at a transcriptional level, resulting in repression of the activatory receptor NKG2D. Alleviating tumor hypoxia reinvigorated NKG2D expression and the antitumor function of gammadelta T cells. These results reveal a hypoxia-mediated mechanism through which brain tumors and gammadelta T cells interact and emphasize the importance of gammadelta T cells for antitumor immunity against brain tumors. |
