| First Author | Dodagatta-Marri E | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 1 | Pages | 109309 |
| PubMed ID | 34233193 | Mgi Jnum | J:320432 |
| Mgi Id | MGI:6874551 | Doi | 10.1016/j.celrep.2021.109309 |
| Citation | Dodagatta-Marri E, et al. (2021) Integrin alphavbeta8 on T cells suppresses anti-tumor immunity in multiple models and is a promising target for tumor immunotherapy. Cell Rep 36(1):109309 |
| abstractText | alphavbeta8 integrin, a key activator of transforming growth factor beta (TGF-beta), inhibits anti-tumor immunity. We show that a potent blocking monoclonal antibody against alphavbeta8 (ADWA-11) causes growth suppression or complete regression in syngeneic models of squamous cell carcinoma, mammary cancer, colon cancer, and prostate cancer, especially when combined with other immunomodulators or radiotherapy. alphavbeta8 is expressed at the highest levels in CD4+CD25+ T cells in tumors, and specific deletion of beta8 from T cells is as effective as ADWA-11 in suppressing tumor growth. ADWA-11 increases expression of a suite of genes in tumor-infiltrating CD8+ T cells normally inhibited by TGF-beta and involved in tumor cell killing, including granzyme B and interferon-gamma. The in vitro cytotoxic effect of tumor CD8 T cells is inhibited by CD4+CD25+ cells, and this suppressive effect is blocked by ADWA-11. These findings solidify alphavbeta8 integrin as a promising target for cancer immunotherapy. |
