In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Immunol. 2022 Jul 1;13:937344. doi: 10.3389/fimmu.2022.937344. eCollection 2022.
Tumor immunotherapy has shown strong therapeutic potential for stimulating or reconstructing the immune system to control and kill tumor cells. It is a promising and effective anti-cancer treatment besides surgery, radiotherapy and chemotherapy. Presently, some immunotherapy methods have been approved for clinical application, and numerous others have demonstrated promising results and have entered clinical trial stages. Although immunotherapy has exhibited encouraging results in various cancer types, however, a large proportion of patients are limited from these benefits due to specific characteristics of the tumor microenvironment such as hypoxia, tumor vascular malformation and immune escape, and current limitations of immunotherapy such as off-target toxicity, insufficient drug penetration and accumulation and immune cell dysfunction. Ultrasound-target microbubble destruction (UTMD) treatment can help reduce immunotherapy-related adverse events. Using the ultrasonic cavitation effect of microstreaming, microjets and free radicals, UTMD can cause a series of changes in vascular endothelial cells, such as enhancing endothelial cells' permeability, increasing intracellular calcium levels, regulating gene expression, and stimulating nitric oxide synthase activities. These effects have been shown to promote drug penetration, enhance blood perfusion, increase drug delivery and induce tumor cell death. UTMD, in combination with immunotherapy, has been used to treat melanoma, non-small cell lung cancer, bladder cancer, and ovarian cancer. In this review, we summarized the effects of UTMD on tumor angiogenesis and immune microenvironment, and discussed the application and progress of UTMD in tumor immunotherapy.
肿瘤免疫疗法通过刺激或重建免疫系统来控制和杀死肿瘤细胞，具有强大的治疗潜力。它是继手术、放疗和化疗之后一种有前途且有效的抗癌治疗方法。目前，一些免疫疗法已被批准用于临床应用，还有许多其他方法已显示出有希望的结果并已进入临床试验阶段。尽管免疫疗法在各种癌症类型中已显示出令人鼓舞的结果，但由于肿瘤微环境的特定特征，如缺氧、肿瘤血管畸形和免疫逃逸，以及免疫疗法目前存在的局限性，如脱靶毒性、药物渗透和积累不足以及免疫细胞功能障碍，很大一部分患者无法从中受益。超声靶向微泡破坏（UTMD）治疗可以帮助减少免疫治疗相关的不良反应。UTMD 利用微流、微射流和自由基的超声空化效应，可以引起一系列血管内皮细胞的变化，如增强内皮细胞的通透性、增加细胞内钙离子水平、调节基因表达和刺激一氧化氮合酶活性。这些作用已被证明可以促进药物渗透、增强血液灌注、增加药物递送并诱导肿瘤细胞死亡。UTMD 联合免疫疗法已被用于治疗黑色素瘤、非小细胞肺癌、膀胱癌和卵巢癌。在这篇综述中，我们总结了 UTMD 对肿瘤血管生成和免疫微环境的影响，并讨论了 UTMD 在肿瘤免疫治疗中的应用和进展。
