免疫检查点抑制剂诱导的大肠炎由多功能淋巴细胞介导,并且依赖IL23/IFNγ轴
Jonathan W Lo1, Domenico Cozzetto1, James L Alexander1
1Division of Digestive Diseases, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
Nature communications
|October 23, 2023
概括
免疫检查点抑制剂 (CPI) 可以引起结肠炎,特别是当它们结合使用时. 这项研究表明,准IL23/IFNγ轴可以通过调节肠道微生物群和淋巴细胞来逆转这种副作用.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 胃肠病学 胃肠病学
背景情况:
- 免疫检查点抑制剂 (CPI),如抗CTLA4和抗PD-1,提供了新的癌症治疗方法.
- 组合CPI疗法提高了疗效,但可能导致免疫媒介组织损伤,特别是在肠道.
- 由CPI引起的肠道平衡破坏是一个重大的临床挑战.
研究的目的:
- 调查抗CTLA4和抗PD-1免疫疗法对肠道恒温的影响.
- 阐明CPI诱导性结肠炎 (CPI-结肠炎) 背后的机制.
- 确定缓解CPI结肠炎的潜在治疗点.
主要方法:
- 使用CPI结肠炎的临床前小鼠模型.
- 与CPI治疗一起操纵肠道微生物群.
- 通过批量RNA测序,单细胞RNA测序和流细胞测量分析结肠免疫特征.
主要成果:
- CPI-结肠炎的发展取决于肠道微生物群的组成.
- CPI-结肠炎的特征是诱导产生干扰素γ (IFNγ) 的淋巴细胞.
- 在CPI结肠炎期间,促炎性细胞因子和化学因子显著上调.
- 在小鼠模型中,IL23/IFNγ轴的阻塞显示出减轻CPI结肠炎的能力.
结论:
- CPI结肠炎是一种微生物群依赖的疾病,由特定的免疫反应驱动.
- 针对IL23/IFNγ轴是一个有希望的治疗策略来管理CPI结肠炎.
- 调节IFNγ产生淋巴细胞或调节网络可以逆转CPI诱导的肠道损伤.
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