Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Adv Exp Med Biol. 2020;1248:119-141. doi: 10.1007/978-981-15-3266-5_6.
Immune checkpoint blockade (ICB) therapy has become a promising way of overcoming cancers, whereas the therapy can induce immunopathology due to the disruption of the immune homeostasis. These adverse events caused by ICB are named as immune-related adverse events (irAEs), which can be severe and life-threaten. Understanding the mechanisms and managements of irAEs is critical for improving the efficacy of immune checkpoint therapy. Immune-related adverse events can occur on various organs, and gastrointestinal tract has the highest rate for severe irAEs. Accumulated evidences indicate the ability of the gut microbiota in regulating the response to immune checkpoint therapy, but the function of microbiota in irAEs remains unclear. T cells, including functional subsets: Th17 T cells and regulatory T (Treg) cells, play significant roles in determining the inflammatory microenvironment. The gut immune tolerance toward dietary antigens and commensals, and anti-inflammatory function in intestines are maintained mainly by Treg cells. Furthermore, tissue residency of functional T cells depends on the homing/trafficking to the locations of inflammation. Here, we review the role of microbiota and the interaction between microbiota and intestinal Treg cells in irAEs, and discuss the function of gut-trafficking blockade antibodies in the context of ICB therapy.
免疫检查点阻断（ICB）疗法已成为克服癌症的一种有前途的方法，然而，由于免疫稳态的破坏，该疗法可引发免疫病理学。这些由 ICB 引起的不良事件被命名为免疫相关不良事件（irAEs），它们可能很严重且危及生命。了解 irAEs 的机制和管理对于提高免疫检查点治疗的疗效至关重要。irAEs 可发生在各种器官上，而胃肠道发生严重 irAEs 的几率最高。大量证据表明肠道微生物群在调节对免疫检查点治疗的反应方面具有能力，但微生物群在 irAEs 中的功能仍不清楚。T 细胞，包括功能亚群：Th17 T 细胞和调节性 T（Treg）细胞，在决定炎症微环境方面发挥着重要作用。肠道对膳食抗原和共生菌的免疫耐受以及肠道的抗炎功能主要由 Treg 细胞维持。此外，功能性 T 细胞的组织驻留取决于向炎症部位的归巢/迁移。在这里，我们综述了微生物群的作用以及微生物群与肠道 Treg 细胞之间的相互作用在 irAEs 中的作用，并讨论了肠道贩运阻断抗体在 ICB 治疗中的作用。
