| First Author | Dao V | Year | 2016 |
| Journal | Cancer Res | Volume | 76 |
| Issue | 20 | Pages | 5970-5982 |
| PubMed ID | 27569211 | Mgi Jnum | J:236245 |
| Mgi Id | MGI:5805583 | Doi | 10.1158/0008-5472.CAN-16-0091 |
| Citation | Dao V, et al. (2016) Immune-Stimulatory Effects of Rapamycin Are Mediated by Stimulation of Antitumor gammadelta T Cells. Cancer Res 76(20):5970-5982 |
| abstractText | The FDA-approved mTOR inhibitor rapamycin mediates important immune effects, but its contributions to the anticancer effects of the drug are unclear. Here we report evidence that rapamycin-mediated cancer protection relies upon stimulation of gammadelta T cells. In a well-established mouse model of carcinogen and inflammation-driven skin carcinogenesis, IFNgamma recruited gammadelta TCRmid T cells to the epidermis where rapamycin boosted their perforin-dependent antitumor properties. These antitumor cells were mostly Vgamma5-Vgamma4-Vgamma1- in phenotype. IFNgamma signals were required in both hematopoietic and nonhematopoietic cells for rapamycin to optimally promote epidermal infiltration of gammadelta TCRmid T cells, as mediated by CXCR3-CXCL10 interactions, along with the antitumor effects of these cells. In mouse xenograft models of human squamous cell carcinoma, rapamycin improved human gammadelta T-cell-mediated cancer cell killing. Our results identify immune mechanisms for the cancer prevention and treatment properties of rapamycin, challenging the paradigm that mTOR inhibition acts primarily by direct action on tumor cells. Cancer Res; 76(20); 5970-82. (c)2016 AACR. |
