灌注不足通常是由于血管构型异常造成的，导致肿瘤缺氧。这种情况的存在阻碍了治疗药物的有效输送和免疫细胞向肿瘤的浸润，从而损害了肿瘤治疗的效果。本研究的目的是利用超声 (US) 的热效应来诱导肿瘤内局部温度升高，从而促进血管舒张、增强药物输送并增强免疫细胞浸润。超声参数的选择基于肿瘤内温度升高及其对细胞活力的影响。使用酶联免疫吸附测定（ELISA）和免疫荧光检查研究血管舒张和缺氧的改善。通过冰冻切片分析、ELISA 和体内荧光成像分析商业聚乙二醇化脂质体阿霉素（PLD）和 PD-L1 抗体（抗 PD-L1）在肿瘤中的分布和积累。使用流式细胞术（FCM）评估肿瘤免疫微环境。通过监测各种治疗后的肿瘤生长和存活率，研究超声增强化疗联合免疫治疗的疗效。0.8 W/cm2 的超声照射条件 10 分钟，有效将肿瘤温度升高至约 40 °C，且不引起任何细胞损伤。或组织损伤，并充分诱导血管舒张，从而增强 PLD 和抗 PD-L1 在 US 治疗的肿瘤中的分布和递送。此外，它能有效缓解肿瘤缺氧，同时显着增加 M1 表型肿瘤相关巨噬细胞 (TAM) 和 CD8 T 细胞，并减少 M2 表型 TAM。通过结合US照射，PLD和抗PD-L1的治疗效果显着提高，从而有效抑制肿瘤生长并延长小鼠的生存期。应用US（0.8 W/cm2，10分钟）可以有效诱导血管舒张并增强 PLD 和抗 PD-L1 向肿瘤的递送，从而重塑免疫抑制肿瘤微环境并优化治疗结果。© 2024 Xiang et al.

The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration.The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments.The US irradiation condition of 0.8 W/cm2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice.The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.© 2024 Xiang et al.