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

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.

RARRES2 is involved in the “lock-and-key” interactions between osteosarcoma stem cells and tumor-associated macrophages

“…In addition, TAMs are involved in crosstalk with CSCs in various types of tumors 61 . M2-type TAMs promote cancer stem-like properties in tumors, including hepatocellular carcinoma 62 , breast cancer 63 , non-small cell lung cancer 64 , pancreatic ductal adenocarcinoma 65 , and glioblastoma multiforme 66 . Mitchum et al showed that ablation of CCR2 or CSF-1R signaling significantly blocked TAM infiltration in pancreatic ductal adenocarcinoma (PDAC), reduced the number of CD44 + ALDH1 + CSCs, and improved the response to chemotherapy 67 .…”

Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

“…Tumors overexpressing PD-L1 are often accompanied by the infiltration of PD-1-positive TILs, which are associated with shortened overall survival, indicating a poor prognosis for breast cancer (Muenst et al 2013 ; Sun et al 2014 ). PD-L1 affects not only T cells but also tumor-associated macrophages, inducing tumor-promoting M2 polarization (Meng et al 2022 ; Zhang R et al 2022 ).…”

Translatomics to explore dynamic differences in immunocytes in the tumor microenvironment

“…TAMs mainly refer to M2-type macrophages, which form an immunosuppressive microenvironment and promote tumor growth and angiogenesis through cytokine production. 79 , 80 As a bridge between innate and adaptive immunity, DCs play a significant role in antigen presentation. 81 It can be seen that immune cells in the TME cannot act alone, and interactions between immune cells may lead to reconstruction of the TME and thus promote or inhibit tumor processes.…”