STAT3 restrains dendritic cell function and tumor immunity

Abstract STAT3 is considered an oncogene in multiple human cancers. However, its direct involvement dendritic cell (DC)-mediated antitumor immunity and immune checkpoint blockade (ICB) remains unknown. Here, we found that was constitutively activated DCs restrained DC function the tumor microenvironment (TME). Genetic ablation of resulted enhanced T immunity, thereby slowing down progression bearing mouse models. Analogously, targeting with a proteasome degradation agent, SD-36, preferentially deleted expression DCs, dependent-T therapeutically synergized ICB tumor-bearing Clinically, combination Stat3 gene signature correlated complete response patients who received ICB. Thus, signaling pathway restrains has potential to promote immunologic TME sensitizing immunotherapy.