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B7 family checkpoint regulators in immune regulation and disease

Sabrina Ceeraz1, Elizabeth C Nowak, Randolph J Noelle

  • 1Geisel School of Medicine at Dartmouth, Department of Microbiology and Immunology, Norris Cotton Cancer Centre, 1 Medical Center Drive, Lebanon, New Hampshire 03756, USA.

Trends in Immunology
|August 20, 2013
PubMed

Insights

Checkpoint regulators like CTLA-4 are crucial for immune response. New B7 family ligands, including VISTA, are emerging as potential therapeutic targets for various diseases.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Immune response fine-tuning involves co-stimulatory and co-inhibitory molecules.
  • Cytotoxic T-lymphocyte antigen 4 (CTLA-4) checkpoint blockade therapy (ipilimumab) is FDA-approved, highlighting the clinical relevance of immune checkpoints.
  • Ongoing trials target CTLA-4, programmed death-1 (PD-1), and B7-H4 pathways.

Purpose of the Study:

  • To review the B7 family of immune checkpoint regulators.
  • To discuss their role in immune response to self and foreign antigens.
  • To explore clinical developments and introduce V-domain Ig suppressor of T cell activation (VISTA) as a therapeutic target.

Main Methods:

  • Literature review of B7 family members.
  • Analysis of immune regulation by B7 ligands.
  • Review of clinical trials targeting immune checkpoints.
  • Introduction of VISTA as a potential therapeutic target.

Main Results:

  • The B7 family comprises multiple inhibitory ligands, including newly identified VISTA and B7-H6.
  • These ligands play a concerted role in regulating T cell activation and immune tolerance.
  • Clinical strategies targeting CTLA-4, PD-1, and B7-H4 are under investigation.

Conclusions:

  • The B7 family significantly impacts immune responses and self-tolerance.
  • Targeting B7 family members offers promising therapeutic avenues for various diseases.
  • VISTA represents a novel and potentially valuable target for immune modulation.

Keywords:
B7 familyco-inhibitory moleculesco-stimulatory molecules

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