光热触发的非亡调节细胞死亡相关途径调节增强了全身抗瘤免疫力
Yanting Liang1,2, Haitao Yuan1,2,3, Qiu Jin1
1Department of Nephrology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital, (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China.
这项研究引入了一种新疗法,将轻度光热疗法与非亡调控细胞死亡 (RCD) 结合起来,以克服瘤抵抗和免疫抑制,增强抗瘤免疫力.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 生物医学工程 生物医学工程
背景情况:
- 瘤细胞对亡和免疫抑制的抵抗阻碍了免疫疗法.
- 轻度光热疗法 (mPTT) 显示出潜力,但受到瘤热耐受性的限制.
- 需要替代细胞死亡途径来重塑免疫抑制瘤微环境 (ITME).
研究的目的:
- 开发一种协同效应的免疫光热疗法,激活非亡调控细胞死亡 (RCD) 模式.
- 为了克服瘤细胞的耐热性,并改造ITME以提高治疗疗效.
- 研究铁和热在增强免疫细胞死亡 (ICD) 中的相互作用.
主要方法:
- 开发一种协同效应的免疫光热疗法剂.
- 在近红外 (NIR) 辐射下诱导活性氧物种 (ROS) 和脂质过氧化 (LPO).
- 对铁,热和热冲击蛋白 (HSP) 抑制的分析.
- RNA测序以识别与RCD途径相关的基因变异.
主要成果:
- 该疗法通过增加ROS,LPO和耗尽谷氨 (GSH) 来有效触发铁亡.
- 铁灭抑制了热冲击蛋白 (HSP),克服了瘤细胞对mPTT的热耐受性.
- 协同效应通过Caspase-1/GSDMD通路激活了热.
- 联合铁和热增强了ICD,重塑了ITME并释放了与损伤相关的分子模式.
结论:
- 开发的疗法克服了mPTT诱导的瘤热耐受性,通过激活非apoptotic RCD.
- 这种方法有效地通过诱导铁亡和热亡来重塑免疫抑制瘤微环境 (ITME).
- 协同激活RCD为增强瘤免疫疗法的疗效提供了一个有希望的策略.
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