PD-L1 Mediates Triple Negative Breast Cancer Evolution by Regulating TAM/M2 Polarization

Abstract Aim This study aimed to explore the role of αPD-L1 (PD-L1 inhibitor) in triple-negative breast cancer (TNBC) cells metastasis and angiogenesis by regulating tumor-associated macrophages (TAMs) polarization and its possible molecular mechanism. Methods The effects of αPD-L1 on tumor metastasis and TAMs polarization were confirmed both in vitro and in vivo. The expression of M2-type macrophages (TAM/M2) and M1-type macrophages (TAM/M1) surface markers were detected by flow cytometry, western blot and IF staining assays. The effects of αPD-L1 on the proliferation and apoptosis of TAM/M2 were detected by MTT and flow cytometry assays. The effects of αPD-L1 on the migration capability of TNBC cells were detected by wound healing and transwell assays. The effects of angiogenesis were detected by endothelial tube formation and western blot assays. The effects of αPD-L1 on epithelial-mesenchymal transition (EMT) process and stemness of TNBC cells were detected by western blot and IF staining assays. The expression and location of STAT3 and p-STAT3 proteins in cells were detected by western blot and IF staining assays. Results In this study, we demonstrated that αPD-L1 significantly inhibited IL-13-induced TAM/M2 polarization in vitro. αPD-L1 inhibited EMT process and stemness of TNBC cells mediated by reversing TAM/M2 polarization, thus inhibiting the migration and angiogenesis of TNBC cells. αPD-L1 prevented STAT3 phosphorylation and nuclear translocation, resulting in TAM/M2 polarization arrest. αPD-L1 reduced the number of lung metastases without affecting tumor growth in vivo. αPD-L1 reduced the expression of TAM/M2, EMT, stemness, and vascular markers in tumor tissues. Conclusions Taken together, these data suggest that αPD-L1 plays a vital role in anti-metastasis and anti-angiogenesis of TNBC in vitro and in vivo by inhibiting TAM/M2 polarization.