title: CD8+ T cells promote proliferation of benign prostatic hyperplasia epithelial cells under low androgen level via modulation of CCL5/STAT5/CCND1 signaling pathway.
abstract: 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.
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Urology, Linyi People's Hospital, Linyi 276003, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Tianjing
authors.initials: T
authors.lastname: Lv
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Wenke
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, University of Rochester Medical Center, Rochester 14642, NY, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing 100034, China.|National Research Center for Genitourinary Oncology, Beijing 100034, China.|Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018946:Chemokine CCL5 / Q000378:metabolism*; D018920:Coculture Techniques; D019938:Cyclin D1 / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D018120:Finasteride / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D010868:Pimozide / Q000494:pharmacology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C483024:CCL5 protein, human; C530104:CCND1 protein, human; D018946:Chemokine CCL5; D050799:STAT5 Transcription Factor; D013196:Dihydrotestosterone; D019938:Cyclin D1; D010868:Pimozide; D018120:Finasteride