Background/Objectives:Preclinical animal studies and clinical case reports have shown evidence of histotripsy being capable of inducing anti-tumor immune responses strong enough to inhibit tumor growth of off-target tumors. Previous studies exploring histotripsy immune stimulation have used a single therapy dose. This study aims to explore how histotripsy dose affects local tumor immune stimulation in a murine melanoma model.Methods:C57BL/6J mice bearing subcutaneous B16F10 tumors were treated with histotripsy using an ultrasound-guided 8-element 1 MHz transducer operating at a 100 Hz pulse repetition frequency (PRF) and >30 MPa peak-negative pressure. The histotripsy dose was defined by the number of pulses (8, 20, 40, or 100) per focal location (ppl). Tissue damage and residual tissue structure were measured histologically and scored by a trained pathologist. The longitudinal effect of histotripsy dosing was assessed using tumor growth and survival. Acute immune stimulation was measured at days 2 and 7 post-treatment via immunofluorescence staining of the treated tumor.Results:Histotripsy doses at 20, 40, and 100 ppl achieved significant tumor necrosis within the target region (>75%), with residual structure decreasing as the dose increased. Overall, the greatest tumor control was observed in mice that received the 40 ppl dose compared to untreated mice. This correlates with the 40 ppl dose also having the largest increase in CD45+ immune cells and CD8+T cells 7 days post-treatment compared to untreated mice.Conclusions:The effect of histotripsy dosing on immune infiltration and tumor growth highlights the significant impact of histotripsy dose on clinical effects.
背景/目的：临床前动物研究和临床病例报告已证实，组织粉碎术能够诱导足够强的抗肿瘤免疫反应，从而抑制非靶向肿瘤的生长。既往探讨组织粉碎术免疫刺激作用的研究均采用单一治疗剂量。本研究旨在探索组织粉碎术剂量如何影响小鼠黑色素瘤模型的局部肿瘤免疫刺激。 方法：采用超声引导的8阵元1 MHz换能器，以100 Hz脉冲重复频率和>30 MPa峰值负压，对携带皮下B16F10肿瘤的C57BL/6J小鼠进行组织粉碎术治疗。组织粉碎术剂量由每个聚焦位点的脉冲数（8、20、40或100）定义。通过组织学方法测量组织损伤和残余组织结构，并由专业病理学家进行评分。采用肿瘤生长和生存期评估组织粉碎术剂量的纵向效应。治疗后第2天和第7天，通过对治疗肿瘤进行免疫荧光染色来测量急性免疫刺激。 结果：20、40和100脉冲/位点的组织粉碎术剂量在靶区内实现了显著的肿瘤坏死（>75%），且残余组织结构随剂量增加而减少。总体而言，与未治疗小鼠相比，接受40脉冲/位点剂量的小鼠表现出最佳的肿瘤控制效果。这与治疗后第7天，40脉冲/位点剂量组小鼠的CD45+免疫细胞和CD8+T细胞增幅最大相关。 结论：组织粉碎术剂量对免疫浸润和肿瘤生长的影响，突显了剂量对临床疗效的重要作用。
肿瘤(癌症)患者之家