1. TET2 promotes anti-tumor immunity by governing G-MDSCs and CD8 + T-cell numbers.
- Author
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Li S, Feng J, Wu F, Cai J, Zhang X, Wang H, Fetahu IS, Iwanicki I, Ma D, Hu T, Liu H, Wang B, Shi G, Tan L, and Shi YG
- Subjects
- Adaptive Immunity, Animals, CD8-Positive T-Lymphocytes, Cell Count, DNA-Binding Proteins genetics, Dioxygenases, Mice, Proto-Oncogene Proteins genetics, Myeloid-Derived Suppressor Cells, Neoplasms genetics
- 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 inhibits syngeneic tumor growth. Collectively, these findings reveal a TET2-mediated IL-6/G-MDSCs/CD8+ T-cell immune response cascade that safeguards host adaptive anti-tumor immunity, offering a cell non-autonomous mechanism of TET2 for tumor suppression., (© 2020 The Authors.)- Published
- 2020
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