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

Autor:	Liu S; Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA., Rivero SL; Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA., Zhang B; Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA.; Medical Laboratory of ShenZhen LuoHu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China., Shen K; Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA., Li Z; Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA.; Hubei University of Medicine, Shiyan, Hubei, China., Niu T; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA., Rowan BG; Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA., Jazwinski SM; John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.; Tulane Center for Aging, Tulane University, New Orleans, LA, USA., Abdel-Mageed AB; Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA., Steele C; Department of Microbiology & Immunology, Tulane University School of Medicine, New Orleans, LA, USA., Wang AR; Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA., Sartor O; Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.; Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA., Zhang Q; Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA.; Tulane Center for Aging, Tulane University, New Orleans, LA, USA.; Tulane Cancer Center and Louisiana Cancer Research Center, Tulane University, New Orleans, LA, USA.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2024 Oct 01; Vol. 116 (10), pp. 1598-1611.
DOI:	10.1093/jnci/djae120
Abstrakt:	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 with IL-23A and IL-23R but not RORC. Conclusion: Our novel findings underscore the crucial role of IL-23-IL-23R signaling in mediating the function of Batf-dependent Th17 cells, thereby promoting prostate cancer initiation and progression. This finding highlights the BATF-IL-23R axis as a promising target for the development of innovative strategies for prostate cancer prevention and treatment. (© The Author(s) 2024. Published by Oxford University Press.)
Databáze:	MEDLINE
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