Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
Shanghai Institute of Immunology, Translational Medicine Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27509-27515. doi: 10.1073/pnas.1921223117. Epub 2020 Oct 19.
Immune checkpoint-blocking antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe immune-related adverse events. Previously, we found that could mitigate intestinal immunopathology in the context of CTLA-4 blockade in mice. Here we examined the mechanism underlying this process. We found that altered the composition of the gut microbiota systematically in a regulatory T cell (Treg)-dependent manner. Moreover, this altered commensal community enhanced both the mitochondrial fitness and the IL-10-mediated suppressive functions of intestinal Tregs, contributing to the amelioration of colitis during immune checkpoint blockade.
免疫检查点阻断抗体可减弱免疫耐受,已被用于有效治疗癌症,但它们也可能引发严重的免疫相关不良反应。此前,我们发现 在 CTLA-4 阻断的情况下可减轻小鼠的肠道免疫病理学。在此,我们研究了这一过程的潜在机制。我们发现 以依赖调节性 T 细胞 (Treg)的方式系统性地改变了肠道微生物组的组成。此外,这种改变的共生群落增强了肠道 Treg 的线粒体适应性和 IL-10 介导的抑制功能,有助于改善免疫检查点阻断期间的结肠炎。