Increased OIT3 in macrophages promotes PD-L1 expression and hepatocellular carcinogenesis via NF-κB signaling

Abstract

Oncoprotein-induced transcript 3 (OIT3) facilitates macrophage M2 polarization and hepatocellular carcinoma (HCC) progression, however, whether OIT3 regulates tumor immunity remains largely unknown. Here we found that OIT3 was upregulated in HCC-associated macrophages, which inhibited CD4⁺ and CD8⁺ T-cell infiltration in the tumor microenvironment (TME). Mechanistically, OIT3 increased the expression of PD-L1 on tumor-associated macrophages (TAMs) by activating NF-κB signaling, blockade of NF-κB reversed the immunosuppressive activity of TAMs and dampens HCC tumorigenesis. Our findings provide the molecular basis for OIT3 enhancing tumor immunosuppression and highlighted a potential therapeutic strategy for targeting the TAMs of HCC.

Keywords: NF-κB signaling; Oncoprotein-induced transcript 3; PD-L1; Tumor associated macrophages; Tumor microenvironment.