Pd42-10 Immunosuppressive Role of BDNF in Therapy-Induced Neuroendocrine Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Markers II (PD42)1 May 2024PD42-10 IMMUNOSUPPRESSIVE ROLE OF BDNF IN THERAPY-INDUCED NEUROENDOCRINE PROSTATE CANCER Yu-Tsan Lin, Yen-Nien Liu, Wei-Yu Chen, and Yu-Ching Wen Yu-Tsan LinYu-Tsan Lin , Yen-Nien LiuYen-Nien Liu , Wei-Yu ChenWei-Yu Chen , and Yu-Ching WenYu-Ching Wen View All Author Informationhttps://doi.org/10.1097/01.JU.0001008560.54103.65.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is a complex disease characterized by heterogeneous molecular alterations and immune evasion mechanisms. Activation of leukemia inhibitory factor (LIF) and its receptor (LIFR) signaling is implicated in the progression of therapy-induced neuroendocrine PCa (tNEPC). We tried to find the role of the LIF/LIFR signaling pathway in regulating the immunosuppressive tumor microenvironment (TME) in PCa cells. METHODS: Normal human prostate epithelial cells and adenocarcinoma PCa cells, NEPC-like cells were obtained and cultured, and a DNA sequence analysis verified all constructs. For coculture treatment, human WMPY-1 prostate stroma cells were counted and seeded, creating coculture conditions for the experiment. Samples stained with the antibody and the images were captured using a fluorescence microscope. Cell proliferation assays, sphere formation assay, migration and invasion through Matrigel assays were conducted. Tumorigenicity assays in mice was conducted. In a double-blind fashion, four 6-week-old male nude mice were subcutaneously injected with 2 106 LNCaP cells. In Enzyme-linked immunosorbent assay (ELISA), serum samples from patients with BPH, HSPC, and CRPC were obtained. BDNF levels were measured with a human BDNF ELISA kit . A standard curve was generated using software capable of constructing a four-parameter logistic fit curve, and BDNF levels in the samples were calculated based on this curve. RESULTS: Our findings demonstrated that activating the LIF/LIFR pathway in PCa after androgen deprivation therapy (ADT) contributed to upregulating the immune checkpoint proteins in PCa cells. Activation of the LIF/LIFR signaling pathway promoted the immunosuppressive phenotype through induction of brain-derived neurotrophic factor (BDNF) in the PCa TME. BDNF abundance is upregulated by LIF/LIFR signaling and promotes neuroendocrine differentiation (NED) and an aggressive phenotype of PCa. High serum levels of BDNF in castration-resistant PCa (CRPC) patients correlated with high BDNF expression in prostate tumors with neuroendocrine features. Patients with high levels of BDNF mRNA exhibited a higher survival rate in response to anti-programmed death-ligand 1 (PDL1) therapy, suggesting that BDNF could serve as a potential biomarker for guiding anti-PDL1 immunotherapy. CONCLUSIONS: Our results suggest that LIF/LIFR signaling is a critical mediator of BDNF and PDL1 expressions in PCa, providing potential prognostic markers and therapeutic targets for combination strategies to overcome the immunosuppressive TME and NED in advanced PCa. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e896 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yu-Tsan Lin More articles by this author Yen-Nien Liu More articles by this author Wei-Yu Chen More articles by this author Yu-Ching Wen More articles by this author Expand All Advertisement PDF downloadLoading ...