High-intensity focused ultrasound ablation to increase tumor-specific lymphocytes in prostate cancer

Abstract

Treatment options for localized prostate cancer have been expanded by FDA-approval of High-Intensity Focused Ultrasound (HIFU). Prostate cancer typically has few tumor-infiltrating lymphocytes, which are crucial for antitumor immunity. This study investigated the use of HIFU to increase lymphocyte infiltration into the tumor and enhance antitumor immunity. RM1 prostate tumors were implanted onto both flanks of syngeneic C57BL/6 J mice, with one tumor subjected to HIFU treatment. The growth of the contralateral tumor was monitored. Blood samples were obtained from patients both before and after prostatectomy or HIFU treatment. Peripheral blood mononuclear cells (PBMCs) were then isolated to analyze the immune cells. In murine experiments, the application of HIFU to one tumor decreased the growth of the contralateral (non-HIFU treated) tumor, when the contralateral tumor was the same tumor type, but not when it was a different tumor type. HIFU increased infiltration of CD4+ and CD8+ lymphocytes into the contralateral, same-type tumor. Lymphocyte depletion studies affirmed that the antitumor immune response triggered by HIFU relies on CD4+ and CD8+ lymphocytes. Addition of cholesterol-lowering intervention further increased antitumor immunity generated by HIFU in mice. In human subjects, HIFU, but not prostatectomy, stimulated anti-tumor CD4+ and CD8+ lymphocytes. We concluded that HIFU induced a potent cellular antitumor immune response that inhibited the progression of murine prostate tumors. HIFU stimulated tumor-specific cellular immunity in patients. Future clinical trials should explore the clinical benefits of HIFU, possibly in combination with existing immunotherapies, as immune modulators for both localized and metastatic disease.

Keywords

• Prostate cancer
• High intensity focused ultrasound
• Tumor immunity
• Cholesterol
• Immunotherapy