Abstract:
Objective To explore the expression of programmed cell death-ligand 1 (PD-L1) of tumor-associated macrophages (TAMs) and its relationship with adverse prognosis of breast cancer.
Methods The expression of PD-L1 in immune cells of 165 breast cancer patients was analyzed by single-cell RNA-sequencing (scRNA-seq) database and tumor immune single-cell hub (TISCH) dataset. Multicolor immunofluorescence was used to detect the expression of PD-L1 in breast cancer TAMs. THP-1 monocytes were induced to m2-type polarization and co-cultured with breast cancer cell lines MCF-7 and MDA-MB-231 for 24 h; the expression of PD-L1 in TAMs was detected by western blot and reverse transcription-polymerase chain reaction (RT-PCR).
Results PD-L1 expression was significantly upregulated in metastatic TAMs compared with primary breast cancer(P < 0.05). The expression of PD-L1 in TAMs was positively correlated with the histological grade of breast cancer (P=0.001), but had no correlation with the patientś age, tumor size, lymph node metastasis, molecular subtype and distant metastasis (P>0.05). High density PD-L1+TAMs infiltration suggested a poor prognosis. When M2-type macrophages were co-cultured with MCf-7 or MDA-MB-231 cell lines, the expression levels of PD-L1 mRNA and PD-L1 protein in TAMs increased.
Conclusion The PD-L1 expression in breast cancer tissue TAMs is significantly positively correlated with histological grade and poor prognosis of breast cancer patients, and breast cancer cells can stimulate PD-L1 expression in M2-type macrophages (the main component of TAMs).
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