Pd35-12 High-Intensity Focused Ultrasound Ablation Increases Lymphocyte Infiltration and Induces Immunogenic Cell Death in Mouse Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III (PD35)1 May 2024PD35-12 HIGH-INTENSITY FOCUSED ULTRASOUND ABLATION INCREASES LYMPHOCYTE INFILTRATION AND INDUCES IMMUNOGENIC CELL DEATH IN MOUSE PROSTATE CANCER Shengchen Su, Yanping Wang, Eric M. Lo, Patrick Tamukong, and Hyung L. Kim Shengchen SuShengchen Su , Yanping WangYanping Wang , Eric M. LoEric M. Lo , Patrick TamukongPatrick Tamukong , and Hyung L. KimHyung L. Kim View All Author Informationhttps://doi.org/10.1097/01.JU.0001009396.21455.74.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: High-Intensity Focused Ultrasound (HIFU) is an FDA-approved procedure for the ablation of prostate tissue. HIFU can destroy tumor tissue by noninvasively delivering ultrasonic energy, which rapidly heats the targeted tissue and induces coagulative necrosis. Immunogenic cell death (ICD) occurs if ablation generates cell signals known as damage-associated molecular patterns (DAMPs), which can initiate an adaptive immune response. Prostate cancer has few tumor-infiltrating lymphocytes, which are required for antitumor immunity. The objective of this study was to determine if HIFU induces immunogenic cell death and activates anti-tumor immunity with increased lymphocyte infiltration into the tumor. METHODS: The HIFU transducer was a 3.5 MHz focused, single-element transducer with a 33mm active diameter and 35mm radius of curvature (SU-107, Sonic Concepts, Bothell, WA). The transducer was connected to a 200 W amplifier (AMP-200, Sonic Concepts, Bothell, WA) and a waveform generator (Agilent 33220A, Agilent Technologies, Santa Clara, CA). RM1 prostate adenocarcinoma cells were treated in vitro with HIFU and cultured for 48 hours. Key DAMP proteins such as calreticulin and HSP 70 were evaluated using western blot. RM1 tumors were grown on the flanks of syngeneic C57BL/6J mice and one tumor was treated with HIFU. Contralateral tumor growth was monitored and tumors were collected at the end of the study to assess immune cell infiltration. Tumor infiltrating lymphocytes were assessed by flow cytometry. RESULTS: In cells treated with HIFU, the expression of HSP 70, calreticulin, and interferon β1 increased over time, suggesting that HIFU induces immunogenic cell death. When one tumor was treated with HIFU, the growth of the contralateral (untreated) tumor decreased when the contralateral tumor was the same tumor type but not when it was a different tumor type. HIFU increased CD4+ and CD8+ lymphocyte infiltration into the contralateral (untreated) tumor. Depletion studies confirmed that the anti-tumor immune effect of HIFU is CD4+ and CD8+ lymphocyte-dependent. CONCLUSIONS: In preclinical models, HIFU induces immunogenic cell death and generates an anti-tumor immune response capable of suppressing the growth of mouse prostate tumors. The anti-tumor immune effect of HIFU is CD4+ and CD8+ lymphocyte-dependent. Future studies should investigate mouse models of metastatic prostate cancer, where cytoreductive prostate tumor ablation can be combined with systemic immunotherapies to generate robust antitumor immunity. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e729 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Shengchen Su More articles by this author Yanping Wang More articles by this author Eric M. Lo More articles by this author Patrick Tamukong More articles by this author Hyung L. Kim More articles by this author Expand All Advertisement PDF downloadLoading ...