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自强化光热免疫调节,增强ISR-ICD级联对手术后复发的作用

Yiming Liu¹, Jiheng Shan², Chengzhi Zhang²

¹Department of Interventional Radiology, Key Laboratory of Interventional Radiology of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, China; Interventional Institute of Zhengzhou University, Zhengzhou, 450001, China; Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.

|January 14, 2026

概括

这项研究提出了一种新的光热疗法策略,使用纳米纤维支架来治疗肝癌复发. 该方法增强抗瘤免疫力,建立长期免疫记忆,提供潜在的临床应用.

科学领域:

在瘤学瘤学.
生物材料科学生物材料科学
免疫治疗是一种免疫疗法.

背景情况:

手术后肝癌复发是一个重要的临床问题.
光热疗法 (PTT) 显示出消除残留癌症和增强抗瘤免疫力的潜力.
瘤细胞通过通过综合应激反应 (ISR) 激活热冲击蛋白90 (HSP90) 来抵抗PTT.

研究的目的:

开发一种自我增强的光热免疫调节策略,以克服肝癌中PTT抵抗.
通过准HSP90激活和诱导免疫细胞死亡 (ICD) 来提高PTT的疗效.
将PTT与免疫疗法协同用于持续的抗瘤反应和免疫记忆.

主要方法:

工程电纳米纤维支架与黑色纳米片 (BPNS) 和HSP90抑制剂 (17-DMAG) 配合装载.
利用近红外 (NIR) 辐射进行PTT和控制药物释放.
研究了诱导亡,ICD和免疫微环境调制 (树突细胞成熟,T细胞初始化).
在临床前模型中评估了与抗PD-L1的联合治疗.

主要成果:

纳米纤维支架有效地将NIR光转化为热,并释放17-DMAG,增强蛋白质毒性.
该策略成功地将ISR从支持生存转向了亡和ICD,增加了瘤免疫性.
与抗PD-L1的联合治疗使T细胞恢复活力,并建立了持久的免疫记忆.
局部治疗有效抑制了术后肝癌复发和转移.

结论:

开发的光热免疫调节策略将PTT与ISR-ICD级联集成,用于增强肝癌治疗.
这种方法克服了PTT耐药性,并与抗PD-L1免疫疗法协同作用.
该策略显示了在治疗术后肝癌复发的临床转化方面具有显著的潜力.

关键词:

免疫检查点抑制剂免疫检查点抑制剂免疫原性细胞死亡综合应激反应综合应激反应光热疗法是一种光热疗法.手术后的肝癌复发情况

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