肿瘤细胞治疗研究
英文原题：Focused ultrasound-triggered doxorubicin liposomes reshape tumor microenvironment to boost checkpoint depletion in triple-negative breast cancer model.
Focused ultrasound-triggered doxorubicin liposomes reshape tumor microenvironment to boost checkpoint depletion in triple-negative breast cancer model.
这些发现表明，将HiFUS与IMP301整合可有效调节TME并增强检查点阻断治疗，支持其在TNBC和其他实体瘤中的转化潜力。
高强度聚焦超声（HiFUS）联合空化响应型脂质体（IMP301）提供了一种增强三阴性乳腺癌（TNBC）免疫治疗疗效的治疗策略。本研究探讨了HIFUS这一非侵入性手段如何重塑肿瘤微环境（TME），将“抑制性”肿瘤转化为“响应性”肿瘤，并提高对免疫检查点阻断（ICB）的敏感性。我们发现，HIFUS可增加血管通透性并诱导免疫原性细胞死亡（ICD），从而实现多柔比星（Dox）从IMP301中的局部释放。在临床前模型中，该治疗改善了免疫浸润，NK细胞、CD8 T细胞和M1巨噬细胞升高，髓源性抑制细胞（MDSCs）减少。抗原特异性T细胞增加约3.1倍（p < 0.0001），长效记忆T细胞可防止转移和复发。值得注意的是，靶向Dox递送将全身毒性降至最低，允许更高剂量且不良反应更少。在肿瘤生长研究中，HIFUS与IMP301联合抗PD1实现了完全缓解，凸显了持久控制癌症的潜力。具体而言，10只小鼠中有4只出现缓解，生存期延长至50天 vs 26天（p < 0.0001）。这些结果表明，将HiFUS与IMP301整合可有效调节TME并增强检查点阻断治疗，支持其在TNBC及其他实体瘤中的转化潜力。
High Intensity Focused Ultrasound (HiFUS) combined with cavitation-responsive liposomes (IMP301) offers a therapeutic strategy to enhance immunotherapy efficacy in triple-negative breast cancer (TNBC). This study investigates how HIFUS, a non-invasive modality, remodels the tumor microenvironment (TME), transforming "suppressive" tumors into "responsive" ones and improving susceptibility to immune checkpoint blockade (ICB). We show that HIFUS increases vascular permeability and induces immunogenic cell death (ICD), enabling localized release of doxorubicin (Dox) from IMP301. In preclinical models, treatment improved immune infiltration, with elevated NK cells, CD8 T cells, and M1 macrophages, and reduced myeloid-derived suppressor cells (MDSCs). Antigen-specific T cells increased ∼3.1-fold (p < 0.0001), and long-lasting memory T cells prevented metastasis and recurrence. Notably, targeted Dox delivery minimized systemic toxicity, permitting higher dosing with fewer adverse effects. In tumor growth studies, the combination of HIFUS and IMP301 with anti-PD1 achieved complete remission, highlighting potential for durable cancer control. Specifically, remission occurred in 4 of 10 mice, with survival extended to 50 vs 26 days (p < 0.0001). These findings demonstrate that integrating HiFUS with IMP301 effectively modulates the TME and enhances checkpoint blockade therapy, supporting its translational potential in TNBC and other solid tumors.
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