High-intensity focused ultrasound ablation increases lymphocyte infiltration in mouse prostate tumor

Abstract Introduction and Objective: High-Intensity Focused Ultrasound (HIFU) is an FDA-approved procedure for the treatment of localized prostate cancer. HIFU destroys tumor tissue by noninvasively delivering ultrasonic energy, which rapidly heats the targeted tissue. Prostate cancer has few tumor-infiltrating lymphocytes, which are required for antitumor immunity. The objective of this study was to determine if HIFU activates antitumor immunity and increases lymphocyte infiltration into the tumor. Methods: 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 assess by flow cytometry. Results: 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 antitumor immune effect of HIFU is CD4 +and CD8 +lymphocyte dependent. Conclusions: In preclinical models, HIFU generates an antitumor immune response capable of suppressing the growth of mouse prostate tumors. The antitumor 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. Homer and Gloria Harvey Family Chair Fund in urologic oncology in honor of Stuart Friedman, M.D.