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Lizhou Lin¹, Xiao Li¹, Wenyun Guo¹

¹Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

Cell reports. Medicine

|March 10, 2026

概括

工程Salmonella细菌释放气囊 (GVs),当被聚焦超声波激活时,重塑固体瘤. 这种方法增强了T细胞的透和功能,改善了采用T细胞治疗的结果.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
生物技术是生物技术.
生物医学工程生物医学工程

背景情况:

固体瘤具有显著的树皮和免疫障碍,阻碍T细胞透和抗瘤活性.
目前的免疫疗法在克服复杂的瘤微环境 (TME) 方面面临着挑战.

研究的目的:

设计一种基于沙门氏菌的新型系统,用于TME的机械改造.
研究LIFUS激活GVs对T细胞功能和瘤控制的影响.
开发一种机械化启动策略,以增强采用性T细胞疗法.

主要方法:

改造的沙门氏菌VNP20009以表达气体囊泡 (GVs).
利用低强度聚焦超声波 (LIFUS) 激活GVs,在瘤内产生局部机械力.
进行单细胞RNA测序以分析T细胞状态和TME组成.
在临床前瘤模型中评估了机械启动方法的有效性.

主要成果:

激活LIFUS的GVs通过减少与癌症相关的纤维细胞 (CAFs) 和矩阵密度来重塑TME.
通过Notch1-Jagged1轴观察到CAF-CD8+T细胞通信的中断.
增强了内CD8+T细胞透,细胞毒性效应器功能和细胞因子的产生.
机械治疗改善了CD8+T细胞细胞毒性,减少了疲劳,并导致了持久的瘤控制和延长生存时间.

结论:

由LIFUS激活的GV为TME的生物力学改造提供了一个新的策略.
这种方法增强了T细胞透和效应器功能,克服了瘤诱导的免疫抑制.
用LIFUS驱动的GV进行机械启动,代表了采用T细胞疗法的有希望的增强.

关键词:

在NOTCH路径上.免疫疗法免疫疗法机械传导机械传导瘤微环境是一个微环境.超声波超声波是指超声波的使用.

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