Department of Urology, Zigong Fourth People's Hospital, 643000 Zigong, Sichuan, China.
Institute of Precision Medicine, Zigong Academy of Big Data and Artificial Intelligence for Medical Science, 643000 Zigong, Sichuan, China.
Arch Esp Urol. 2024 May;77(4):322-330. doi: 10.56434/j.arch.esp.urol.20247704.44.
High intensity focused ultrasound (HIFU), also referred to as focused ultrasound surgery (FUS), has garnered recent attention as a non-invasive therapeutic strategy for prostate cancer. It utilizes focused acoustic energy to achieve localized thermal ablation, while also potentially exerting immunomodulatory effects. This review aims to elucidate the mechanisms underlying how HIFU influences tumor-specific immune responses in prostate cancer. These mechanisms include the release of tumor-associated antigens and damage-associated molecular patterns, the activation of innate immune cells, the facilitation of antigen presentation to adaptive immune cells, the enhancement of activation and proliferation of tumor-specific cytotoxic T lymphocytes, and the attenuation of the immunosuppressive tumor microenvironment by reducing the activity of regulatory T cells and myeloid-derived suppressor cells. Both preclinical investigations and emerging clinical data in prostate cancer models highlight HIFU's potential to modulate the immune system, as evidenced by increased infiltration of effector immune cells, elevated levels of pro-inflammatory cytokines, and improved responsiveness to immune checkpoint inhibitors. HIFU induces immunogenic cell death, leading to the release of tumor antigens and danger signals that activate dendritic cells and facilitate cross-presentation to cytotoxic T cells. Additionally, FUS ablation reduces immunosuppressive cells and increases infiltration of CD8 T cells into the tumor, reshaping the tumor microenvironment. By priming the immune system while overcoming immunosuppression, combining FUS with other immunotherapies like checkpoint inhibitors and cancer vaccines holds promise for synergistic anti-tumor effects. Despite challenges in optimizing parameters and identifying suitable patients, FUS represents a novel frontier by modulating the tumor microenvironment and enhancing anti-tumor immunity through a non-invasive approach.
高强度聚焦超声（HIFU），也称为聚焦超声手术（FUS），最近作为一种非侵入性的前列腺癌治疗策略引起了关注。它利用聚焦声能实现局部热消融，同时还可能发挥免疫调节作用。本综述旨在阐明 HIFU 如何影响前列腺癌中肿瘤特异性免疫反应的机制。这些机制包括肿瘤相关抗原和损伤相关分子模式的释放、固有免疫细胞的激活、抗原呈递给适应性免疫细胞的促进、肿瘤特异性细胞毒性 T 淋巴细胞的激活和增殖的增强，以及通过减少调节性 T 细胞和髓源性抑制细胞的活性来减轻免疫抑制性肿瘤微环境。临床前研究和前列腺癌模型中的新兴临床数据均强调了 HIFU 调节免疫系统的潜力，这表现在效应免疫细胞的浸润增加、促炎细胞因子水平升高以及对免疫检查点抑制剂的反应性改善。HIFU 诱导免疫原性细胞死亡，导致肿瘤抗原和危险信号的释放，激活树突状细胞并促进细胞毒性 T 细胞的交叉呈递。此外，FUS 消融减少了免疫抑制细胞并增加了 CD8 T 细胞浸润到肿瘤中，重塑了肿瘤微环境。通过在克服免疫抑制的同时启动免疫系统，将 FUS 与免疫检查点抑制剂和癌症疫苗等其他免疫疗法相结合，有望产生协同的抗肿瘤作用。尽管在优化参数和确定合适患者方面存在挑战，但 FUS 通过非侵入性方法调节肿瘤微环境和增强抗肿瘤免疫，代表了一个新的前沿。
