B7x—from bench to bedside

Gurbakhash Kaur

Murali Janakiram

^{Department of Medical Oncology, Albert Einstein College of Medicine, New York city, New York, USA}

^{Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA}

^{Corresponding author.}

^{Dr Murali Janakiram;}ude.nmu@rikanajm

Received 2019 Jun 4; Revised 2019 Aug 12; Accepted 2019 Aug 14.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, any changes made are indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Abstract

B7x is an immune checkpoint molecule which belongs to the B7 family of ligands which includes PD-L1, PD-L2, B7-H3 and HHLA2. B7x belongs to the Immunoglobulin superfamily and its protein structure is similar to other members with a N terminus peptide, IgV and IgC like extracellular domain with four cysteine residues. Its receptor is yet to be identified. B7x inhibits T cell proliferation and expansion by IL-2 dependent and non-IL-2 dependent pathways. Even though high levels of B7x mRNA can be detected in most tissues its protein expression is highly limited suggesting significant post translational control. In vivo data, show that B7x plays an important role in limiting autoimmunity in the peripheral tissues and fine-tuning autoimmune responses. B7x is highly expressed in various cancers and in prostate cancer its expression is corelated with poorer outcomes. Local production of IL-6 and IL-10 in various cancers promotes B7x expression and tumor immune evasion. B7x is especially expressed in PD-L1 negative tumors suggesting that this may be an important method of immune evasion in these tumors. Currently drug development, targeting B7x through various mechanisms including monoclonal antibodies and antibody drug conjugates are in development in cancers and increasing B7x expression with fusion proteins in autoimmune diseases is underway.

Keywords: B7x, B7-H4, VTCN1, B7S1, B7 homolog 4, novel immune checkpoints, immunotherapy, immune checkpoint blockade

Abstract

Footnotes

Contributors: GK and MJ: Writing, design, analysis and final submission.

Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests: None declared.

Patient consent for publication: Not required.

Provenance and peer review: Commissioned; externally peer reviewed.

Footnotes

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