Integrin Alpha V Beta 8 On T Cells Suppresses Anti-Tumor Immunity In Multiple Models And Is A Promising Target For Tumor Immunotherapy

alpha v beta 8 integrin, a key activator of transforming growth factor beta(TGF-beta), inhibits anti-tumor immunity. We show that a potent blocking monoclonal antibody against alpha v beta 8 (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. alpha v beta 8 is expressed at the highest levels in CD4+CD25+ T cells in tumors, and specific deletion of beta 8 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-g. 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 alpha v beta 8 integrin as a promising target for cancer immunotherapy.