Abstract：
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.
摘要：
高强度聚焦超声(HIFU)也称为聚焦超声手术（FUS），作为前列腺癌的非侵入性治疗策略，最近引起了人们的关注。它利用聚焦声能实现局部热消融，同时也可能发挥免疫调节作用。这篇综述旨在阐明HIFU如何影响前列腺癌中肿瘤特异性免疫反应的潜在机制。这些机制包括肿瘤相关抗原的释放和损伤相关的分子模式，先天免疫细胞的激活，促进抗原呈递到适应性免疫细胞，增强肿瘤特异性细胞毒性T淋巴细胞的活化和增殖，以及通过降低调节性T细胞和骨髓来源的抑制细胞的活性来减弱免疫抑制性肿瘤微环境。前列腺癌模型中的临床前研究和新出现的临床数据都突出了HIFU调节免疫系统的潜力。正如效应免疫细胞浸润增加所证明的那样，促炎细胞因子水平升高，并改善对免疫检查点抑制剂的反应。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交叉呈递到细胞毒性T细胞。此外,FUS消融可减少免疫抑制细胞并增加CD8+T细胞向肿瘤的浸润，重塑肿瘤微环境。通过启动免疫系统，同时克服免疫抑制，将FUS与其他免疫疗法如检查点抑制剂和癌症疫苗相结合，有望产生协同抗肿瘤作用。尽管在优化参数和确定合适的患者方面存在挑战，FUS代表了通过非侵入性方法调节肿瘤微环境和增强抗肿瘤免疫力的新前沿。
