PD-1 (Programmed death-1) is mainly expressed on the surface of T cells and primary B cells. The two PD-1 ligands, PD-L1 and PD-L2, are widely expressed on antigen-presenting cells (APCs). PD-L1 expression is favorable for tumorigenesis and growth, for induction of anti-tumor T cell apoptosis, and for escaping responses by the immune system. Inhibition of PD-1 binding to its ligand can result in tumor cell killing by the immune system, and thus is a target for cancer treatments. CD276 (Cluster of Differentiation 276) is a human protein encoded by the CD276 gene and belongs to the immunoglobulin superfamily. The transcript of B7-H3 is ubiquitously expressed in normal tissues and solid tumors, while the protein is preferentially expressed only in tumor tissues. B7-H3 is expressed on immune cells (such as antigen-presenting cells or macrophages) and has inhibitory roles on T cells, contributing to tumor cell immune evasion. Importantly, B7-H3 is highly overexpressed on a wide range of human solid cancers and often correlates with both negative prognosis and poor clinical outcome in patients. Recent studies have shown that B7-H3 is a crucial player in tumor growth, invasion, migration, angiogenesis and metastasis beyond the immune regulatory roles. Due to its role in immune evasion, B7-H3 has become an interesting target for new immunotherapeutic treatments. B7-H3 and PD-L1 induce an inhibitory effect on T-cells and change their microenvironment to escape the anti-tumor immune response. B7-H3 and CTLA-4 may act synergistically with one another, just as B7-H3 does in the PD-1 pathway.
Protein expression analysis in T cells
Strain specific PD-1 expression analysis in homozygous B-hPD-1/hB7-H3 (H/H) mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hB7-H3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-PD-1 antibody. Mouse PD-1 was detectable in WT mice. Human PD-1 was exclusively detectable in homozygous B-hPD-1/hB7-H3 but not WT mice.
Strain specific analysis of B7-H3 expression in WT and B-hPD-1/hB7-H3 mice by western blot. Epididymis were collected from WT (+/+) mice and homozygous B-hPD-1/hB7-H3 mice. Mouse B7-H3 was detectable in WT mice. Human B7-H3 was detectable in the epididymis of B-hPD-1/hB7-H3 mice due to the cross-reactivity of antibodies.