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 language | English (US) |
---|---|
Pages (from-to) | 40-51 |
Number of pages | 12 |
Journal | Immunological Reviews |
Volume | 276 |
Issue number | 1 |
DOIs | |
State | Published - Mar 1 2017 |
Funding
This work was supported in part by NMSS grant RG 4624A10/1 and funding from Amplimmune, Inc. The authors do not have any conflicts of interest regarding this work.
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