PD‑L1 mediates triple‑negative breast cancer evolution via the regulation of TAM/M2 polarization

Tumor-associated macrophages/M2-type (TAM/M2) play a key role in the metastasis and angiogenesis of cancer, and are considered to be critical targets for cancer treatment. However, it remains unclear whether alpha-programmed death-ligand 1 (alpha PD-L1; PD-L1 inhibitor) inhibits tumor progression via targeting TAMs. In the present study, it was demonstrated that alpha PD-L1 significantly inhibited IL-13-induced TAM/M2 polarization in vitro. Moreover, alpha PD-L1 inhibited the epithelial-mesenchymal transition (EMT) process and the stemness of triple-negative breast cancer (TNBC) cells, which were mediated via the reversal of TAM/M2 polarization. This therefore inhibited the migration and angiogenesis of TNBC cells. Furthermore, alpha PD-L1 prevented STAT3 phosphorylation and nuclear translocation, which resulted in the arrest of TAM/M2 polarization. In vivo experiments further demonstrated that alpha PD-L1 reduced the number of lung metastases without affecting tumor growth. Moreover, alpha PD-L1 reduced the expression levels of TAM/M2, EMT, stemness and vascular markers in tumor tissues. In summary, these data suggest that alpha PD-L1 plays a vital role in the anti-metastasis and anti-angiogenesis of TNBC in vitro and in vivo via the inhibition of TAM/M2 polarization. These findings may thus provide a novel therapeutic strategy for clinically refractory TNBC.