CD276 molecule | Elisa - Clia - Antibody - Protein

Background

CD276, also known as B7-H3, is a protein encoded by the CD276 gene located on chromosome 15q24.1. It is a member of the B7 family of immune regulatory molecules, which are known to play crucial roles in the modulation of immune responses. B7-H3 was first identified in 2001 and has since been recognized for its involvement in immune regulation, particularly in the context of cancer, autoimmunity, and transplantation.

The expression of B7-H3 is widespread, found on various cell types, including dendritic cells, monocytes, activated T cells, and several non-immune cells such as fibroblasts, endothelial cells, and certain epithelial cells. Its expression can be induced by inflammatory cytokines and other immune signals. The exact function of B7-H3 in the immune system has been a subject of ongoing research, with evidence suggesting both co-stimulatory and co-inhibitory roles depending on the context.

Protein Structure

The B7-H3 protein is a type I transmembrane glycoprotein. It exists in two isoforms generated through alternative splicing: a shorter form with two immunoglobulin-like (Ig-like) domains (2Ig-B7-H3) and a longer form with four Ig-like domains (4Ig-B7-H3). Both isoforms have an extracellular domain, a transmembrane region, and a short cytoplasmic tail.

• Extracellular Domain: The extracellular region of B7-H3 contains the Ig-like V and C domains, which are characteristic of the B7 family members. These domains are crucial for the protein’s interaction with its receptor(s) on immune cells.
• Transmembrane Region: This segment anchors B7-H3 in the cell membrane.
• Cytoplasmic Tail: The cytoplasmic tail, though short, is implicated in intracellular signaling. However, the exact signaling pathways influenced by the cytoplasmic tail of B7-H3 are not yet fully understood.

The structural variations between the 2Ig and 4Ig forms suggest potential differences in their functional roles and interactions with other molecules.

Classification and Subtypes

B7-H3 belongs to the B7 family of immune regulatory proteins, which includes other members such as B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1), B7-DC (PD-L2), and B7-H4. These proteins are known for their roles in providing either stimulatory or inhibitory signals to T cells, thus modulating immune responses.

As of now, B7-H3 itself does not have subtypes in the classical sense but exists in different isoforms (2Ig-B7-H3 and 4Ig-B7-H3), which may have distinct biological functions.

Function and Biological Significance

B7-H3 plays multifaceted roles in the immune system and beyond:

1. Immune Regulation: B7-H3 can function as both a co-stimulatory and co-inhibitory molecule. In some contexts, it enhances T cell responses and promotes anti-tumor immunity. In others, it inhibits T cell activation and proliferation, contributing to immune evasion by tumors.
2. Tumor Biology: B7-H3 is often overexpressed in various cancers, including breast, lung, prostate, and colorectal cancers. Its expression is associated with poor prognosis, increased tumor invasiveness, and resistance to therapy. Tumors exploit B7-H3 to suppress anti-tumor immune responses, facilitating their growth and metastasis.
3. Angiogenesis and Metastasis: Beyond immune modulation, B7-H3 promotes angiogenesis (the formation of new blood vessels) and metastasis. It supports the survival and proliferation of endothelial cells, thereby aiding tumor vascularization.
4. Autoimmunity and Inflammation: B7-H3 is involved in regulating autoimmune responses. Its expression is upregulated in inflammatory conditions, where it modulates the activity of various immune cells, potentially limiting tissue damage.
5. Transplantation: In the context of organ transplantation, B7-H3 has been shown to influence graft acceptance and rejection. Its role in regulating T cell responses can impact the outcome of transplantation, making it a potential target for improving graft survival.

Clinical Issues

The clinical implications of B7-H3 are vast, particularly in oncology and immunotherapy:

1. Cancer Immunotherapy: Targeting B7-H3 with monoclonal antibodies and other therapeutic agents is being explored as a strategy to enhance anti-tumor immunity. Several B7-H3 inhibitors are currently in preclinical and clinical development, aiming to block its immune-suppressive functions and improve patient outcomes.
2. Prognostic Marker: High B7-H3 expression in tumors is often correlated with poor prognosis. Measuring B7-H3 levels could serve as a prognostic biomarker to identify patients with more aggressive disease and guide treatment strategies.
3. Autoimmune Diseases: Given its role in modulating immune responses, B7-H3 is a potential target for treating autoimmune diseases. Modulating B7-H3 activity could help restore immune balance and reduce pathological immune responses.
4. Transplantation: In transplantation, strategies to manipulate B7-H3 expression or function could improve graft acceptance and longevity by modulating immune responses.

Summary

The CD276 molecule, or B7-H3, is a versatile immune regulatory protein with significant roles in both promoting and inhibiting immune responses. Its dual functionality is context-dependent, contributing to its involvement in various physiological and pathological processes, including cancer, autoimmunity, and transplantation. B7-H3's overexpression in numerous cancers and its association with poor prognosis make it a promising target for cancer immunotherapy. Understanding the precise mechanisms of B7-H3’s actions and its interactions with other immune regulatory molecules is crucial for developing effective therapeutic interventions. As research progresses, targeting B7-H3 holds potential for improving outcomes in cancer treatment, autoimmune diseases, and transplantation.