Single‐Cell and Spatial Transcriptomics Uncover Immune Dynamics and Cellular Heterogeneity in Benign Prostatic Hyperplasia and Prostate Cancer Transition

Prostate cancer (PCa) is frequently accompanied by benign prostatic hyperplasia (BPH), highlighting the need to reassess their correlation in tumor risk, malignant progression, and immune status to improve the early diagnosis and treatment of PCa. In this study, single-cell RNA sequencing and spatial transcriptomics were used to analyze the potential association between normal, BPH, and PCa tissues. Our study revealed a continuous transformation map of luminal epithelial cells from hyperplasia to malignancy in BPH and PCa, accompanied by a persistently suppressive immune microenvironment. In the lesion nodules, T cells showed a high degree of infiltration yet showed activation retardation and functional exhaustion. Macrophages were also significantly infiltrated, exhibiting significant M2 polarization characteristics, and inflammatory signaling pathways related to immune escape were activated. Natural killer (NK) cells and B cells were partially activated, yet the low abundance of NK cells and B cells resulted in functional limitations. Our results revealed the dynamic changes of the immune landscape during the occurrence and progression of PCa. Our classification and prognostic models provide a theoretical basis for immunomodulatory and personalized therapies and provide new tools for the early diagnosis and intervention of PCa.