Transcriptomic characteristics of tumorassociated macrophages in the microenvironment of triple-negative breast cancer depending on PD-L1 status

Objective: to characterize the transcriptomic features of CD68+ and CD163+ macrophage clusters within the tumor microenvironment of patients with triple-negative breast cancer (TNBC), depending on the PD-L1 status of the tumor. Material and Methods. Eleven patients with TNBC were included in the study. PD-L1 status was assessed by immunohistochemistry. Spatial transcriptomic profiling was performed using the Visium 10x Genomics platform. Cluster annotation for CD68+ and CD163+ cells was carried out in Loupe Browser 8.0.0. Differential gene expression and pathway enrichment analysis were performed for CD68+ and CD163+ clusters in PD-L1-positive and PD-L1-negative groups. Results. PD-L1-positive tumors showed compensatory recruitment of immune cells with features of functional exhaustion, in which CD68+ macrophages were involved. In contrast, PD-L1-negative tumors were characterized by an active adaptive immune response, with CD68+ macrophages functioning as antigen-presenting cells, together with evidence of negative regulation of inflammation associated with CD163+ macrophages. Conclusion. The functional state of macrophages and other cellular components of the TNBC microenvironment varies significantly with PD-L1 status. These results may contribute to the identification of biomarkers for predicting immunotherapy response in this patient group.