在检查点封锁后,EDIL3作为免疫排除的血管性标
Saba Tabasum1,2,3, Dinesh Thapa1,2,3, Anita Giobbie-Hurder3,4
1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Cancer immunology research
|September 20, 2023
概括
在响应癌症免疫治疗的患者中发现了一种针对EGF类重复和迪斯科丁I类域蛋白3 (EDIL3) 的新型抗体反应. 高的EDIL3水平与预后不佳和免疫排除相关,这表明它是治疗目标.
科学领域:
- 免疫学和癌症生物学
- 瘤微环境和血管生成
背景情况:
- 免疫检查点封锁 (ICB) 是一种标准的癌症治疗方法,但其疗效可以通过组合策略来提高.
- 将抗血管原剂与ICB结合起来是有希望的,但潜在的机制需要进一步阐明.
- 类似EGF的重复和类似迪斯科丁I的域蛋白3 (EDIL3) 与各种癌症的预后不佳有关.
研究的目的:
- 研究抗血管原剂和ICB在癌症治疗中的协同作用的机制基础.
- 确定与对组合免疫疗法的良好反应相关的新生物标志物和治疗点.
主要方法:
- 对患者血清进行查,以检测患者对伊皮利穆马布和贝瓦西祖马布的反应者对细胞外蛋白的抗体反应.
- 生物信息分析包括瘤免疫功能障碍和排除 (TIDE),TCGA-SKCM和CheckMate 064数据.
- 在体外研究使用患者衍生的癌症相关纤维细胞 (CAF) 和瘤内皮细胞 (TEC) 进行3D微流体和2D传递试验.
主要成果:
- 在ICB和抗血管原治疗的良好结果的患者中发现了针对EDIL3的高位抗体反应.
- 较高的EDIL3水平与免疫排斥特征,纤维细胞中TGFβ信号的增加,血管新生以及上皮转移到介质细胞的过渡有关.
- 通过干扰LFA-1/ICAM-1相互作用,EDIL3被证明可以增强血管生成并破坏T细胞迁移,从而导致免疫排除.
结论:
- EDIL3在促进免疫抑制瘤微环境和阻碍ICB疗效方面发挥着重要作用.
- 针对EDIL3可以克服免疫排斥并提高免疫检查点阻塞疗法的有效性.
- 循环中的EDIL3水平可以作为对联合免疫疗法的反应的预测生物标志物.
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