MOLECULAR PROFILE OF MACROPHAGES IN PROSTATIC CARCINOMA

Abstract

Objectives. Tumor-associated macrophages (TAMs) are central components of the prostate cancer (PCa) microenvironment. Their molecular phenotypes influence tumor progression, immune evasion, and therapy resistance. This review synthesizes recent evidence on macrophage molecular profiles in prostatic carcinoma, emphasizing emerging biomarkers, signaling pathways, and therapeutic implications.

Methods. A comprehensive literature search was performed in PubMed, Web of Science, and Google Scholar for the years 2000–2025, following PRISMA 2020 guidelines. Eligible studies included those addressing molecular, transcriptomic, or immunohistochemical characteristics of TAMs in human or experimental PCa models. Data extraction focused on macrophage subsets, surface and intracellular markers, and pathway-level mechanisms.

Results. TAMs in PCa display heterogeneous polarization beyond the classical M1/M2 paradigm. Single-cell RNA sequencing and spatial transcriptomics have identified distinct AR⁺TREM2⁺ macrophage subpopulations expressing CD163, APOE, IL10, TGFB1, and PD-L1, which promote immune suppression and tumor growth. Regulatory pathways including CSF-1/CSF-1R, CCL2/CCR2, STAT3, PI3K/AKT, and androgen-receptor signaling coordinate macrophage recruitment and reprogramming. Lipid metabolism and hypoxic cues further reinforce an M2-like phenotype. Clinically, high infiltration of CD163⁺/CD206⁺ macrophages correlate with advanced Gleason grade, biochemical recurrence, and reduced overall survival.

Conclusions. Prostate TAMs are molecularly diverse and clinically relevant modulators of tumor behavior. Therapeutic strategies aimed at modulating TAM signaling (CSF-1R, TREM2, AR) or reprogramming macrophage metabolism may restore antitumor immunity and enhance the efficacy of immune checkpoint blockade. Integrating single-cell profiling with translational studies is crucial for identifying prognostic biomarkers and developing macrophage-targeted interventions.