Previous studies by our group have shown that low intra-prostatic dihydrotestosterone (DHT) induced BPH epithelial cells (BECs) to recruit CD8+ T cells. However, the influence of the recruited CD8+ T cells on BECs under a low androgen level is still unknown. Here, we found CD8+ T cells have the capacity to promote proliferation of BECs in low androgen condition. Mechanism dissection revealed that interaction between CD8+ T cells and BECs through secretion of CCL5 might promote the phosphorylation of STAT5 and a higher expression of CCND1 in BECs. Suppressed CCL5/STAT5 signals via CCL5 neutralizing antibody or STAT5 inhibitor Pimozide led to reverse CD8+ T cell-enhanced BECs proliferation. IHC analysis from Finasteride treated patients showed PCNA expression in BECs was highly correlated to the level of CD8+ T cell infiltration and the expression of CCL5. Consequently, our data indicated infiltrating CD8+ T cells could promote the proliferation of BECs in low androgen condition via modulation of CCL5/STAT5/CCND1 signaling. The increased secretion of CCL5 from the CD8+ T cells/BECs interaction might help BECs survive in a low DHT environment. Targeting these signals may provide a new potential therapeutic approach to better treat BPH patients who failed the therapy of 5α-reductase inhibitors.
Scientific reports. 2017 Feb 20*** epublish ***
Yang Yang, Shuai Hu, Jie Liu, Yun Cui, Yu Fan, Tianjing Lv, Libo Liu, Jun Li, Qun He, Wenke Han, Wei Yu, Yin Sun, Jie Jin
Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China., Department of Urology, Linyi People's Hospital, Linyi 276003, Shandong, China., Department of Radiation Oncology, University of Rochester Medical Center, Rochester 14642, NY, USA.