Different metabolic paradigms and distribution of regulatory T cells between primary and lymph node metastasis prostate cancer.

OBJECTIVE: The objectives of the study are to investigate the differential metabolic paradigms and distribution of regulatory T (Tregs) cells between primary prostate cancer (PCa) and lymph node (LN) metastases. MATERIAL AND METHODS: Single-cell RNA sequencing analysis of primary PCa and LN metastases was employed to reveal the immune infiltration, identify Treg cell clusters, and analyze their metabolic regulation. Immunohistochemical (IHC) for FOXP3 and cluster of differentiation antigen 45 was used to verify different distribution and infiltration of Treg cells. RESULTS: Immune cell infiltration was prominent around PCa cells, with Tregs significantly enriched in node-positive samples, suggesting an immunosuppressive microenvironment. Three Treg subsets were identified: Inhibitory Tregs, effector Tregs, and double-positive Tregs, each exhibiting distinct metabolic profiles. IHC confirmed higher Treg infiltration in LN metastases compared to primary tumors, particularly within tumor stroma. CONCLUSION: Tregs promote lymphatic metastasis in PCa through metabolic reprogramming, with their infiltration levels serving as a potential biomarker for metastatic risk.