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阻断CD73可以通过STING通路强化放射治疗的抗瘤免疫力和abscopal效应

Ran An¹, Chao Wu², Cunyu Tang¹

¹Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin and Tianjin's Clinical Research Center for Cancer, Tianjin, PR China.

Cell death discovery

|September 16, 2024

概括

放射治疗 (RT) 在结直肠癌 (CRC) 中增加CD73,阻碍免疫力. 将RT与CD73封锁结合起来,可以逆转这种免疫抑制,增强CD8+T细胞的反应并改善抗瘤免疫力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
癌症研究癌症研究

背景情况:

放射治疗 (RT) 对结直肠癌 (CRC) 至关重要,但往往无法刺激全身抗瘤免疫力.
免疫调节酶CD73在CRC中在RT后升级,与患者预后不佳相关.

研究的目的:

在CRC中研究RT诱导的CD73上调的机制.
在CRC模型中评估结合RT与CD73阻断在增强免疫反应和abscopal效应方面的疗效.

主要方法:

使用流式细胞计,免疫光和西部血栓检测来分析CD73表达和免疫细胞透.
RNA测序评估了组合治疗对免疫路径的影响.
用CRC皮下瘤模型来测试组合治疗的疗效.

主要成果:

由RT诱导的CD73上调是通过ATR途径调节的,并且与RT耐受性有关.
组合疗法减少了免疫抑制细胞 (MDSCs,TAMs,Tregs) 和增加了免疫刺激细胞 (DCs,CD8+ T细胞).
该组合通过cGAS-STING和IFN-I通路增强了DC抗原呈现和CD8+T细胞激活,从而产生了优异的抗瘤反应.

结论:

将RT与CD73阻断结合起来,可以有效地逆转瘤微环境在CRC中的免疫抑制.
这一策略增强了CD8+T细胞驱动的抗瘤免疫力,为CRC提供了一个有前途的治疗方法.

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