向加勒-9以克服免疫抑制并加强ATR抑制剂治疗
Delong Liu1, Boning Liu2, Riyao Yang3
1Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, P. R. China; Department of Lung Cancer Surgery, Center of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Cancer letters
|February 6, 2026
概括
ATR抑制剂 (ATRi) 可以增加加勒-9 (Gal-9),这通过阻碍免疫反应来限制它们的抗癌作用. 与ATRi疗法一起阻断Gal-9可以增强抗瘤活性和免疫记忆.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 向阿塔克西亚 (telangiectasia) 和Rad3相关激酶 (ATR) 是一种关键的抗癌策略.
- ATR抑制剂 (ATRi) 具有免疫调节作用,但限制其有效性的免疫逃避机制尚未完全理解.
研究的目的:
- 为了研究ATR抑制剂的免疫逃避机制.
- 探索新的组合策略,以提高ATRi的疗效.
主要方法:
- 研究了ATRi对瘤细胞和抗原呈现细胞中加勒-9 (Gal-9) 表达的作用.
- 利用合成基因小鼠模型来评估组合疗法.
- 评估免疫细胞的激活,分化和功能能力.
主要成果:
- 通过STING型I干扰子通路,ATRi可以调节高素-9 (Gal-9).
- 将Gal-9阻塞与ATRi (ceralasertib) 结合起来,显示出强大的抗瘤作用和诱导免疫记忆.
- 三重组合的ATRi,抗Gal-9和抗PD-1提高了免疫检查点耐药肺癌的疗效.
结论:
- 加勒-9的上调是针对ATRi的关键适应性免疫抵抗机制.
- 阻断Gal-9与ATRi协同作用,以增强由CD8+T细胞介导的抗瘤免疫力.
- 针对ATR,Gal-9和PD-1的组合疗法对癌症治疗具有前途.
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