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B7x-from bench to bedside.

Gurbakhash Kaur1, Murali Janakiram1,2

  • 1Department of Medical Oncology, Albert Einstein College of Medicine, New York city, New York, USA.

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Summary

B7x, an immune checkpoint molecule, inhibits T cell responses and is implicated in autoimmunity and cancer immune evasion. Targeting B7x shows promise for cancer therapies and autoimmune disease treatments.

Keywords:
B7 homolog 4B7-H4B7S1B7xVTCN1immune checkpoint blockadeimmunotherapynovel immune checkpoints

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Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • B7x is a B7 family immune checkpoint ligand with structural similarities to other Ig superfamily members.
  • Its receptor remains unidentified, but B7x inhibits T cell proliferation via IL-2 dependent and independent pathways.

Purpose of the Study:

  • To elucidate the role of B7x in immune regulation, autoimmunity, and cancer.
  • To explore B7x as a therapeutic target in cancer and autoimmune diseases.

Main Methods:

  • Analysis of B7x mRNA and protein expression.
  • In vivo studies on B7x function in autoimmunity.
  • Correlation of B7x expression with cancer outcomes.
  • Review of current therapeutic strategies targeting B7x.

Main Results:

  • B7x protein expression is tightly regulated post-translationally despite high mRNA levels.
  • In vivo, B7x limits peripheral autoimmunity and fine-tunes immune responses.
  • High B7x expression in cancers, particularly prostate cancer, correlates with poor prognosis.
  • B7x contributes to tumor immune evasion, especially in PD-L1 negative tumors, through IL-6 and IL-10 induction.

Conclusions:

  • B7x is a critical regulator of immune responses with a dual role in autoimmunity and cancer.
  • B7x represents a significant therapeutic target for both cancer immunotherapy and autoimmune disease management.
  • Ongoing drug development includes monoclonal antibodies, antibody-drug conjugates for cancer, and fusion proteins for autoimmune diseases.