The B7x Immune Checkpoint Pathway: From Discovery to Clinical Trial

Trends Pharmacol Sci. 2019 Nov;40(11):883-896. doi: 10.1016/j.tips.2019.09.008. Epub 2019 Oct 31.

Abstract

B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a broad spectrum of human cancers, where it suppresses antitumor immunity. Further, B7x and PD-L1 tend to have mutually exclusive expression in cancer cells. Therapeutics targeting B7x are effective in animal models of cancers and autoimmune disorders, and early-phase clinical trials are underway to determine the efficacy and safety of targeting B7x in human diseases. It took 15 years moving from the discovery of B7x to clinical trials. Further studies will be necessary to identify its receptors, reveal its physiological functions in organs, and combine therapies targeting B7x with other treatments.

Keywords: B7x; autoimmunity; cancer; immune checkpoint; immunotherapy; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / administration & dosage
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology*
  • Clinical Trials, Phase I as Topic
  • Humans
  • Immune Tolerance
  • Models, Molecular
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Randomized Controlled Trials as Topic
  • Signal Transduction
  • Translational Research, Biomedical
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / antagonists & inhibitors*
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / chemistry
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / immunology*

Substances

  • Antineoplastic Agents, Immunological
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human
  • Vtcn1 protein, mouse