Inhibition of integrin alpha-V/beta-6 sparks T-cell anti-tumor response and enhances immune checkpoint blockade therapy in colorectal cancer. Mus musculus

Integrin alpha-V/beta-6 is a heterodimeric cell surface protein whose cellular expression is determined by the availability of the integrin beta 6 subunit (ITGB6). It is expressed at very low levels in most organs during tissue homeostasis but shows highly upregulated expression during the process of tumorigenesis in many cancers of epithelial origin. Notably, enhanced expression of integrin alpha-V/beta-6 is associated with aggressive disease and poor prognosis in numerous carcinoma entities. Integrin alpha-V/beta-6 is one of the major physiological activators of transforming growth factor-beta (TGF-beta), which has been shown to inhibit the anti-tumor T-cell response and cause resistance to immunotherapy in mouse models of colorectal and mammary cancer. In this study, we investigated the effect of ITGB6 expression and antibody-mediated integrin alpha-V/beta-6 inhibition on the tumor immune response in colorectal cancer.