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

Meng,Ziqi; Zhang,Rui; Wu,Xuwei; Zhang,Meihua; Jin,Tiefeng

doi:10.3892/ijo.2022.5440

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

Authors:
- Ziqi Meng
- Rui Zhang
- Xuwei Wu
- Meihua Zhang
- Tiefeng Jin
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Affiliations: Department of Pathology and Cancer Research Center, Yanbian University Hospital, Yanji, Jilin 133002, P.R. China, Health Examination Centre, Yanbian University Hospital, Yanji, Jilin 133002, P.R. China
Published online on: October 17, 2022 https://doi.org/10.3892/ijo.2022.5440
Article Number: 150
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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