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

PD-L1通过调节TAM/M2极化介导三阴性乳腺癌的演变

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作者:Ziqi Meng ,Rui Zhang ,Xuwei Wu ,Meihua Zhang ,Tiefeng Jin

Abstract

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 α‑programmed death‑ligand 1 (αPD‑L1; PD‑L1 inhibitor) inhibits tumor progression via targeting TAMs. In the present study, it was demonstrated that αPD‑L1 significantly inhibited IL‑13‑induced TAM/M2 polarization in vitro. Moreover, αPD‑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, αPD‑L1 prevented STAT3 phosphorylation and nuclear translocation, which resulted in the arrest of TAM/M2 polarization. In vivo experiments further demonstrated that αPD‑L1 reduced the number of lung metastases without affecting tumor growth. Moreover, αPD‑L1 reduced the expression levels of TAM/M2, EMT, stemness and vascular markers in tumor tissues. In summary, these data suggest that αPD‑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.

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