Potential targeting of B7-H4 for the treatment of cancer

Joseph R. Podojil, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalReview article

30 Scopus citations

Abstract

Observations noting the presence of white blood cell infiltrates within tumors date back more than a century, however the cellular and molecular mechanisms regulating tumor immunity continue to be elucidated. The recent successful use of monoclonal antibodies to block immune regulatory pathways to enhance tumor-specific immune responses for the treatment of cancer has encouraged the identification of additional immune regulatory receptor/ligand pathways. Over the past several years, a growing body of data has identified B7-H4 (VTCN1/B7x/B7S1) as a potential therapeutic target for the treatment of cancer. The potential clinical significance of B7-H4 is supported by the high levels of B7-H4 expression found in numerous tumor tissues and correlation of the level of expression on tumor cells with adverse clinical and pathologic features, including tumor aggressiveness. The biological activity of B7-H4 has been associated with decreased inflammatory CD4+ T-cell responses and a correlation between B7-H4-expressing tumor-associated macrophages and FoxP3+ regulatory T cells (Tregs) within the tumor microenvironment. Since B7-H4 is expressed on tumor cells and tumor-associated macrophages in various cancer types, therapeutic blockade of B7-H4 could favorably alter the tumor microenvironment allowing for antigen-specific clearance tumor cells. The present review highlights the therapeutic potential of targeting B7-H4.

Original languageEnglish (US)
Pages (from-to)40-51
Number of pages12
JournalImmunological Reviews
Volume276
Issue number1
DOIs
StatePublished - Mar 1 2017

Keywords

  • B7-H4
  • B7-H4 receptor
  • CD4 T cell
  • cancer
  • co-stimulatory/co-inhibitory molecule
  • regulatory T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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