| First Author | Li S | Year | 2020 |
| Journal | EMBO Rep | Volume | 21 |
| Issue | 10 | Pages | e49425 |
| PubMed ID | 32929842 | Mgi Jnum | J:301081 |
| Mgi Id | MGI:6505168 | Doi | 10.15252/embr.201949425 |
| Citation | Li S, et al. (2020) TET2 promotes anti-tumor immunity by governing G-MDSCs and CD8(+) T-cell numbers. EMBO Rep 21(10):e49425 |
| abstractText | 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. |
