STAT3 Inhibitor Suppresses CCL2-dependent Recruitment and M2 Polarization of Tumor-associated Macrophages to Enhance Antitumor Immunity in Ovarian Cancer.

Ovarian cancer is a common malignant tumor that severely compromises patient health. STAT3 inhibitor has been widely explored and exhibits therapeutic impacts in diverse cancers. However, the regulatory influences of STAT3 inhibitor on antitumor immunity in ovarian cancer progression need further explorations. The protein expressions were confirmed through IHC assay and western blot. The cell migration was examined through Transwell assay. The protein levels of genes were measured using ELISA. The positive cell was confirmed through flow cytometry. The tumor size, volume and weight were confirmed through in vivo assay. The cell apoptosis was assessed through TUNEL assay. In this study, it was found that STAT3 expression was closely associated with tumor-associated macrophages (TAMs) infiltration based on TCGA database. Moreover, STAT3 inhibitor inhibited macrophage recruitment and M2 macrophage polarization. STAT3 inhibitor suppressed CCL2-dependent recruitment and M2 polarization. Furthermore, macrophages treated with STAT3 inhibitor strengthened antitumor immunity. Finally, through rescue assays, macrophages treated with STAT3 inhibitorimproved the efficiency of PD-1 treatment. In conclusion, STAT3 inhibitor suppressed CCL2-dependent recruitment and M2 polarization of TAMs to enhance antitumor immunity in ovarian cancer. This discovery suggested that STAT3 inhibitor may be used for antitumor immunity in clinical treatment of ovarian cancer.