B7-H4(also known as B7‑S1, B7x and VCTN1)

B7-H4 is a type I transmembrane protein and has 20–30% amino acid homology in the extracellular portion with other B7 family members. It has potential diagnostic and prognostic capacities for identifying cancer, determining pathologic variables, and predicting response to treatment and survival.

Background


An Overview of B7-H4

An important negative regulator of the immunoglobulin B7 family is the B7-H4. B7-H4 protein consists of 282 amino acids. The extracellular amino acids share 20% ~ 30% homology with other members of B7. The main biological function of B7-H4 is the inhibition of immune response. The inhibition of T cell mediated immune response by B7-H4 is generally through three ways: one is to inhibit T cell proliferation, the other is to inhibit T cell activity, and the third is to inhibit cytokines such as IL-2 secretion. B7-H4 inhibited the secretion of IL-10 and IFN-γ, and inhibited the proliferation and activity of CD4+ T cells and CD8+ T cells. The specific antibody blocked B7-H4 and promoted T cell immune response. B7-H4 expression was also detected in the blood of tumor patients, and the soluble B7-H4 also inhibited T cell mediated immune response. Mice with B7-H4 deficiency could form normal CTL reaction in antiviral infection, and their antitumor immune reaction was stronger than that in normal mice.

Inhibition of B7-H4

B7-H4 can be inhibited by some pharmacological drugs at multiple steps. The changes of B7-H4 content in subcellular components before and after treatment with LY294002 were detected by western blot method. The results showed that the content of B7-H4 in cell membrane and cytoplasm decreased significantly after 24h treatment.

B7-H4 and Diseases

B7-H4 binding with the corresponding ligands as a negative regulatory signal of immune response plays an important role in immunosuppressive microenvironment. Detection of B7-H4 expression in rectal cancer patients revealed that the positive rate of B7-H4 protein was as high as 90.6%. The high expression of B7-H4 can be used as a marker for the occurrence of many kinds of tumors, which provides a target for the prevention and treatment of tumor. If we can find out what causes the high expression of B7-H4 in tumor tissues and how the high expression of both can affect the occurrence and development of tumor, we can intervene from these aspects to provide a new way for tumor treatment.

Reference:

Wang Hui, Tian Bo, etc. A. (2013). Research Progress of PD-L1 and B7-H4 in B7 Family. Chinese Journal of Cellular and Molecular Immunology. 29 (02);216-217