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Molecular Events Behind Adverse Effects

  • Shan Sun
  • Feng WangEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1248)

Abstract

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.

Keywords

IrAEs Microbiota Intestinal T cells T cell metabolism T cell homing 

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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of Immunology and Microbiology, Shanghai Institute of ImmunologyShanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Research Center of Translational Medicine, Shanghai Children’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

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