Oral IL-10 suppresses colon carcinogenesis via elimination of pathogenicCD4 T-cells and induction of antitumor CD8 T-cell activity.

An oral sustained-release formulation of Interleukin-10 suppressed tumor growth and enhanced survival in the APC/ spontaneous colon cancer model. Therapeutic benefit was associated with a 5-fold reduction in CD4RORγtFoxp3IL-17 T-helper cell, CD4RORγtFoxp3IL-17 pathogenic T-regulatory cell and CD4RORγtFoxp3IL-17 conventional T-regulatory cell numbers and a concurrent 2-fold enhancement in CD8 T-cell activity in the colon. Selective subset depletion and functional blockade studies demonstrated that at steady-state CD4RORγtIL-17 T-cell subsets and CD4Foxp3 cTreg supported tumorigenesis, whereas CD8 cytotoxic T-lymphocytes impeded tumor progression following IL-10 therapy. Suppression of tumor growth by CD8 T-cells was associated with enhanced tumor infiltration and cytotoxic granule exocytosis. These findings establish the utility of oral IL-10 as a potential new therapeutic in the management of colon cancer and shed light on the cellular mechanisms that underlie its antitumor activity.