CD276

What is CD276 protein?

CD276 (CD276 molecule) gene is a protein coding gene which situated on the long arm of chromosome 15 at locus 15q24. The protein encoded by this gene belongs to the immunoglobulin superfamily, and thought to participate in the regulation of T-cell-mediated immune response. Studies show that while the transcript of this gene is ubiquitously expressed in normal tissues and solid tumors, the protein is preferentially expressed only in tumor tissues. Additionally, it was observed that the 3' UTR of this transcript contains a target site for miR29 microRNA, and there is an inverse correlation between the expression of this protein and miR29 levels, suggesting regulation of expression of this gene product by miR29. The CD276 protein is consisted of 534 amino acids and its molecular mass is approximately 57.2 kDa.

What is the function of CD276 protein?

CD276 acts as an immune checkpoint molecule and is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. CD276 is implicated in the regulation of glucose uptake and metabolism in tumor cells, supporting the Warburg effect, which is a metabolic characteristic of cancer cells. CD276 promotes angiogenesis by stimulating the secretion of vascular endothelial growth factor (VEGF), which is crucial for the growth and survival of tumors. While CD276 mRNA is broadly expressed in various tissues, protein expression is not ubiquitous, suggesting post-transcriptional regulation mechanisms. CD276 is a highly glycosylated protein, and its post-translational modifications, such as glycosylation, are important for its function and stability on the cell surface.

Fig1. The central role of B7-H3 on factors regulating tumor cell plasticity and tumorigenicity. (Elizabeth Varghese, 2024)

CD276 Related Signaling Pathway

CD276 has been shown to interact with the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway, which is known to regulate cell survival, growth, and metabolism. Activation of this pathway by CD276 can lead to the suppression of immune cell activity and promotion of tumor cell survival. CD276 is mentioned as an immune checkpoint molecule in the epithelial-mesenchymal transition (EMT) pathway, which is involved in the development and metastasis of carcinomas. CD276 has been linked to the regulation of metabolic pathways in tumor cells, which can support tumor growth and survival through altered energy metabolism. CD276 deletion in TAMs leads to downregulation of chemokine signaling pathways, which are important for immune cell recruitment and infiltration into the tumor.

CD276 Related Diseases

CD276 is highly expressed in bladder cancer and is linked to poorer overall survival and progression-free survival in patients. Its expression is associated with diminished tumor-infiltrating lymphocytes and hastened cancer progression. Targeting CD276 has shown potential as a therapeutic strategy for bladder tumors. CD276 expression on tumor-associated endothelial cells in ovarian carcinoma is associated with poor patient outcomes. D276 is mentioned in the context of asthma, where it is associated with allergic diseases and the immune response. CD276 is associated with neuroblastoma, which is a cancer that arises from nerve cells, and is linked to the development and differentiation of neural crest cells. CD276 may play a role in this immune condition that occurs after a bone marrow transplant.

Bioapplications of CD276

CD276 blockade in combination with other immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4, is being explored to enhance the efficacy of cancer immunotherapy, particularly in tumors that do not respond well to single-agent treatments. Due to its elevated expression in various solid tumors and its role in promoting an immunosuppressive tumor microenvironment, CD276 is being explored as a therapeutic target. Monoclonal antibodies and bispecific antibodies targeting CD276 are being developed to disrupt its immunosuppressive functions.