Structures of immune checkpoints: An overview on the CD28-B7 family

Weifeng Liu, Xingxing Zang

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations

Abstract

The co-stimulation and co-inhibition signal pathways, immune checkpoints, are among the central mechanisms to regulate the T-cell immunity. Optimal signals involve intricate interactions of numerous ligands and receptors. Manipulation of these signals offers great clinical opportunities and has revolutionized the cancer treatment therapies. The 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo in recognition of their discovery of cancer immunotherapy by inhibition of immune checkpoint molecules. Despite the landmark discovery in cancer immunotherapy, the efforts to harness immunity against cancer are also restricted by the limited knowledge on the co-stimulation and co-inhibition signaling networks. Understanding the structures of these molecules, in particular, tackling the interaction paradigms from the structural perspective, help to provide more accurate insights into the signaling mechanisms, which may further facilitate the development of novel biologics and improve the efficacy of the existing biologics against these targets. Here we review our current understanding on the structures of these co-stimulatory and co-inhibitory molecules. Specifically, we focus on the structural basis of several checkpoint molecules among the CD28-B7 family and discuss the therapeutic drugs against these targets for the treatment of human cancers, autoimmune disorders, and transplantation.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages63-78
Number of pages16
DOIs
StatePublished - 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1172
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • CD28-B7 family
  • Co-inhibition
  • Co-stimulation
  • Immune checkpoint
  • Immunotherapy
  • Structures

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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