TET3 Promotes Tumor Immune Evasion Through Negative Regulation of Type I Interferon Signaling [ChIP-Seq]

However, the functional role of TET3 in cancer immunity and the underlying molecular mechanisms remain incompletely understood. Here, we reported that TET3 restrains the innate immune response in MCF7 and B16F10 cells.

Mechanistically, TET3 does not influence the generation of endogenous dsRNA but represses the expression of major dsRNA sensor genes (i.e., MDA5 and RIG-I) as well as the activation of JAK-STAT1 pathway. Importantly, depletion of Tet3 in B16F10 melanoma cells significantly curbed the synergistic tumor growth, accompanied with increased proportion of tumor-infiltrating CD4+ T cells, CD8+ T cells and dendritic cells. Analysis of the TCGA data also revealed elevated expression of TET3 in most types of cancer.