PLX307609

GSE144787: TET2 promotes anti-tumor immunity by governing G-MDSCs and CD8+ T cell numbers

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Host immune response is a fundamental mechanism for attenuating cancer progression. Here we report a pivotal role of the DNA demethylase and tumor suppressor TET2 played in host antitumor immunity. Deletion of Tet2 dramatically elevated the IL-6 level in Tet2-/- mice upon tumor challenge. The elevated IL-6 greatly stimulated the immunosuppressive granulocytic myeloid-derived suppressor cells (G-MDSCs), which in turn significantly reduced CD8+ T cells upon tumor challenge. Consequently, systematic knockout of the Tet2 in mice led to accelerated syngeneic tumor growth, which was constrained by anti-PD-1 blockade. Removal of G-MDSCs by the anti-mouse Ly6g Ab restored the numbers of CD8+ T cells in Tet2-/- mice and rebooted their anti-tumor activity. Importantly, anti-IL-6 Ab treatment blocked the expansion of G-MDSCs and inhibited syngeneic tumor growth. Collectively, these findings reveal a TET2-mediated IL-6/G-MDSC/CD8+ T immune response cascade that safeguards host adaptive anti-tumor immunity, offering a cell non-autonomous mechanism of TET2 for tumor suppression. SOURCE: Feizhen Wu (wufz@fudan.edu.cn) - Epigenetics lab Fudan Univ, Shanghai, China