Su Shengchen, Wang Yanping, Lo Eric M, Tamukong Patrick, Kim Hyung L
Department of Urology, Cedars Sinai Medical Center, 8635 W. Third St, 1070, Los Angeles, CA 90048, United States.
Department of Urology, Cedars Sinai Medical Center, 8635 W. Third St, 1070, Los Angeles, CA 90048, United States.
Transl Oncol. 2025 Mar;53:102293. doi: 10.1016/j.tranon.2025.102293. Epub 2025 Jan 24.
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.
美国食品药品监督管理局（FDA）批准高强度聚焦超声（HIFU）用于治疗局限性前列腺癌，从而扩大了其治疗选择范围。前列腺癌通常很少有肿瘤浸润淋巴细胞，而这些细胞对抗肿瘤免疫至关重要。本研究调查了使用HIFU增加淋巴细胞浸润到肿瘤中并增强抗肿瘤免疫力的情况。将RM1前列腺肿瘤接种到同基因C57BL / 6 J小鼠的双侧，对其中一个肿瘤进行HIFU治疗。监测对侧肿瘤的生长情况。在前列腺切除术或HIFU治疗前后采集患者的血液样本。然后分离外周血单核细胞（PBMC）以分析免疫细胞。在小鼠实验中，当对侧肿瘤为相同肿瘤类型时，对一个肿瘤应用HIFU可降低对侧（未接受HIFU治疗）肿瘤的生长，但当对侧肿瘤为不同肿瘤类型时则不然。HIFU增加了CD4 +和CD8 +淋巴细胞浸润到对侧的同类型肿瘤中。淋巴细胞清除研究证实，HIFU引发的抗肿瘤免疫反应依赖于CD4 +和CD8 +淋巴细胞。添加降胆固醇干预措施进一步增强了HIFU在小鼠中产生的抗肿瘤免疫力。在人类受试者中，HIFU而非前列腺切除术刺激了抗肿瘤CD4 +和CD8 +淋巴细胞。我们得出结论，HIFU诱导了有效的细胞抗肿瘤免疫反应，抑制了小鼠前列腺肿瘤的进展。HIFU在患者中刺激了肿瘤特异性细胞免疫。未来的临床试验应探索HIFU的临床益处，可能与现有免疫疗法联合使用，作为局部和转移性疾病的免疫调节剂。
