BATF-dependent Th17 cells act through the IL-23R pathway to promote prostate adenocarcinoma initiation and progression

作者：Sen Liu, Seleste L Rivero, Bing Zhang, Keyi Shen, Zixuan Li, Tianhua Niu, Brian G. Rowan, S. Michal Jazwinski, Asim B. Abdel‐Mageed, Chad Steele, Alun R. Wang, Oliver Sartor, Qiuyang Zhang · 发表于：JNCI Journal of the National Cancer Institute · 年份：2024 · DOI：10.1093/jnci/djae120 · 被引用次数：11 · 研究领域：Psoriasis: Treatment and Pathogenesis、Dermatology and Skin Diseases、T-cell and B-cell Immunology

BACKGROUND: The role of Th17 cells in prostate cancer is not fully understood. The transcription factor BATF controls the differentiation of Th17 cells. Mice deficient in Batf do not produce Th17 cells. METHODS: In this study, we aimed to characterize the role of Batf-dependent Th17 cells in prostate cancer by crossbreeding Batf knockout mice with mice conditionally mutant for Pten. RESULTS: We found that Batf knockout mice had changes in the morphology of prostate epithelial cells compared with normal mice, and Batf knockout mice deficient in Pten (called Batf-) had smaller prostate size and developed fewer invasive prostate adenocarcinomas than Pten-deficient mice with Batf expression (called Batf+). The prostate tumors in Batf- mice showed reduced proliferation, increased apoptosis, decreased angiogenesis and inflammatory cell infiltration, and activation of nuclear factor-κB signaling. Moreover, Batf- mice showed significantly reduced interleukin 23 (IL-23)-IL-23R signaling. In the prostate stroma of Batf- mice, IL-23R-positive cells were decreased considerably compared with Batf+ mice. Splenocytes and prostate tissues from Batf- mice cultured under Th17 differentiation conditions expressed reduced IL-23/IL-23R than cultured cells from Batf+ mice. Anti-IL-23p19 antibody treatment of Pten-deficient mice reduced prostate tumors and angiogenesis compared with control immunoglobulin G-treated mice. In human prostate tumors, BATF messenger RNA level was positively correlated w...