Exploding immune cells may explain why prostate drug therapy fails in some

A mechanistic study in Experimental & Molecular Medicine suggests why some men don’t respond to 5-alpha-reductase inhibitors for benign prostatic hyperplasia. The researchers, from Peking University First Hospital and collaborators, report that the drug may trigger a cascade in prostate epithelial cells: immune-cell pyroptosis, neighboring cell senescence, and cellular reprogramming into a drug-tolerant state. Led by Zheng Li, Zhenan Zhang, Qiancheng Zhao, Zhenpeng Zhu, with senior authors Wei Yu and Qian Zhang, the team combined spatial transcriptomics, single-cell RNA sequencing, immunohistochemistry in 50 patients, cell-culture perturbations, and mouse genetics. Spatial transcriptomics analyzed 14 tissue sections and retained 46,176 mapped spots after quality control, identifying shifts in immune and epithelial populations after treatment.