Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies

Cell Mol Immunol. 2023 Jul;20(7):694-713. doi: 10.1038/s41423-023-01019-8. Epub 2023 Apr 17.

Abstract

The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases. Recent basic and clinical studies have revealed novel biology of the B7/CD28 families and new therapeutics for cancer therapy. In this review, we discuss the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways, PD-1/PD-L1 and B7-H3 as metabolic regulators, the glycobiology of PD-1/PD-L1, B7x (B7-H4) and B7-H3, and the recently characterized PD-L1/B7-1 cis-interaction. We also cover the tumor-intrinsic and -extrinsic resistance mechanisms to current anti-PD-1/PD-L1 and anti-CTLA-4 immunotherapies in clinical settings. Finally, we review new immunotherapies targeting B7-H3, B7x, PD-1/PD-L1, and CTLA-4 in current clinical trials.

Keywords: B7 family; glycobiology; immune checkpoints; metabolic regulators; therapy resistance.

Publication types

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

MeSH terms

  • B7-H1 Antigen / metabolism
  • Biology
  • CD28 Antigens* / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Immunotherapy
  • Neoplasms* / therapy

Substances

  • CD28 Antigens
  • B7-H1 Antigen
  • HHLA2 protein, human
  • Immunoglobulins