TRANSCRIPTOMIC HETEROGENEITY OF MONOCYTES AND ITS CONTRIBUTION TO THE FORMATION OF THE IMMUNE MICROENVIRONMENT IN PROSTATE CANCER

Our current knowledge of the transcriptomic characteristics of monocyte populations in prostate cancer remains very limited. This is due to the complexity of studying heterogeneous circulating immune cells, which is caused by the variability of cell phenotypes and antigen expression in tumors. The use of single-cell sequencing provides an opportunity to study the transcriptional profile of monocytes, which may help answer many questions related to the role of different monocyte subpopulations in the formation of the tumor immune microenvironment in patients with prostate cancer.

The aim of the study was to characterize the contribution of transcriptional features of monocyte subpopulations to the formation of the immune microenvironment in prostate cancer.

The study included 3 patients with acinar adenocarcinoma of the prostate and 1 patient with small acinar adenocarcinoma of the prostate. The transcriptomic profile of peripheral blood monocyte cells was obtained using single-cell RNA sequencing (scRNA-seq). Counting matrices were obtained using Cell Ranger and analyzed in R/Seurat, taking into account duplicates (scDblFinder) and filtering low-quality cells. After normalization (SCTransform), integration (Harmony), and clustering (UMAP, PCA, FindClusters), clusters were annotated in Azimuth, and ligand–receptor interactions were explored using CellChat.

Transcriptome profiling of monocyte cells using single-cell RNA sequencing (scRNA-seq) revealed that among the highly expressed genes of classical monocytes, there is a network aimed at increasing the level of proinflammation in the immune environment (S100A8, S100A9, IL-6). Non-classical monocytes were characterized by increased TRPC6, NO/cGMP signaling components (GUCY1A1/B1), and Sema3A, which are associated with angiogenesis, monocyte recruitment, and their polarization into immunosuppressive phenotypes. Intermediate monocytes demonstrated activation of regulatory-migratory programs (ETS1, CCL5) along with elements of T-cell interaction (CD3E, CD247, SKAP1) and IL signaling. The signaling profiles of monocyte subpopulations in prostate cancer show diversity in both outgoing and incoming pathways, reflecting their functional heterogeneity. Features associated with the activation of TGFβ-, galectin-, and TRAIL-signaling are noted, indicating the involvement of different monocyte subtypes in the formation of intercellular interactions in the tumor microenvironment.

Thus, the analysis emphasizes the important role of transcriptional features of monocyte subpopulations in the organization of intercellular interactions and the formation of the immune microenvironment in prostate cancer.

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