TET2 promotes anti-tumor immunity by governing G-MDSCs and CD8⁺ T-cell numbers.

ABSTRACT: The host immune response is a fundamental mechanism for attenuating cancer progression. Here we report a role for the DNA demethylase and tumor suppressor TET2 in host anti-tumor immunity. Deletion of Tet2 in mice elevates IL-6 levels upon tumor challenge. Elevated IL-6 stimulates immunosuppressive granulocytic myeloid-derived suppressor cells (G-MDSCs), which in turn reduce CD8⁺ T cells upon tumor challenge. Consequently, systematic knockout of Tet2 in mice leads to accelerated syngeneic tumor growth, which is constrained by anti-PD-1 blockade. Removal of G-MDSCs by the anti-mouse Ly6g antibodies restores CD8⁺ T-cell numbers in Tet2^-/- mice and reboots their anti-tumor activity. Importantly, anti-IL-6 antibody treatment blocks the expansion of G-MDSCs and

SUBMITTER: Li S 

PROVIDER: S-EPMC7534639 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature