Abstract

Immunotherapies have been widely applied to the treatment of hepatocellular carcinoma (HCC), but to date only a minority of patients exhibit dramatic responses. Tumor-associated macrophages (TAMs) are vital components in the tumor microenvironment and are involved in HCC progression. Herein, we confirm the upregulation of PCBP1 expression in TAMs correlates with poor prognosis in HCC patients. The loss of PCBP1 in TAMs promotes M1 like macrophages polarization and suppresses the migration capability of HCC cells in vitro . Additionally, overexpression of PCBP1 increases M2 macrophage infiltration and promotes tumor growth in vivo . Mechanistically, PCBP1 negatively regulates autophagy flux induction in TAMs to hinder STAT6 degradation from autophagy pathway, thereby facilitating M2-like macrophage phenotype and HCC malignant progression. Collectively, our findings describe the role of PCBP1 in orchestrating TAMs polarization and suggest that blocking PCBP1 is an effective approach in combating the cancerous advancement of HCC.