主体ANGPTL2建立了一个免疫抑制瘤微环境,并对免疫检查点治疗产生抵抗力
Shinsei Yumoto1,2, Haruki Horiguchi1,3, Tsuyoshi Kadomatsu1,4
1Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Cancer science
|September 25, 2024
概括
宿主血管类蛋白2 (ANGPTL2) 驱动免疫检查点抑制剂 (ICI) 的癌症免疫治疗的耐药性. ANGPTL2 缺陷通过减少免疫抑制细胞和炎症,特别是肥胖症,提高 ICI 疗效.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 代谢性疾病 代谢性疾病
背景情况:
- 免疫检查点抑制剂 (ICI) 是关键的癌症免疫疗法,但抵抗机制仍然不完全理解.
- 此前已经报告了血管蛋白样蛋白2 (ANGPTL2) 的促进瘤的功能.
- 宿主因素显著影响瘤免疫类型和对治疗的反应.
研究的目的:
- 研究宿主ANGPTL2在ICI治疗耐药性的作用.
- 探索ANGPTL2缺乏对抗瘤ICI活性在炎症背景的影响.
- 阐明 ANGPTL2 影响瘤微环境和 ICI 响应性的机制.
主要方法:
- 利用大肠直肠癌的小鼠同基因模型.
- 使用高脂肪饮食 (HFD) 诱导的肥胖症的小鼠模型.
- 评估了系统性ANGPTL2缺乏对ICI疗效和瘤免疫微环境的影响.
- 分析了脂肪组织中的细胞因子生产和髓质衍生抑制细胞 (MDSC) 的产生.
主要成果:
- 系统性ANGPTL2缺乏在结直肠癌模型中增强了ICI疗效.
- ANGPTL2在脂肪组织中诱导促炎性细胞因子的产生.
- ANGPTL2驱动MDSC的产生,有助于免疫抑制瘤微环境和ICI耐药性.
- 由HFD诱导的肥胖症降低了ICI反应能力,与慢性炎症和升高的ANGPTL2有关.
结论:
- 主体ANGPTL2在介导ICI治疗的耐药性方面发挥着至关重要的作用.
- ANGPTL2通过脂肪组织炎症和MDSC扩张促进免疫抑制性瘤微环境.
- 由ANGPTL2加剧的肥胖引起的炎症阻碍了ICI的抗瘤作用.
- 针对宿主 ANGPTL2 可能代表克服 ICI 抵抗的策略.
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