CD276 (B7-H3) signal pathway and function
Early studies found that CD276 can promote the activation of T cells. Chapoval et al. confirmed that in the presence of anti-CD3 antibodies, CD276 can promote the proliferation of CD4 and CD8+ T cells and selectively promote the secretion of IFN-γ. Moreover, the transfection of CD276 into tumor cells will enhance the killing ability of CTL. Further research found that only TLT-2 transgenic cells can bind to mouse CD276 with high affinity, confirming that TLT-2 is a receptor molecule for CD276. And Hashiguchi et al. confirmed that the CD276-TLT-2 pathway can enhance the activation of T cells. However, Leitner et al. used flow cytometry to find no specific binding between CD276 and TLT-2. Therefore, the exact receptor molecule of CD276 is still unclear.
On the other hand, studies have found that CD276 can also suppress T cell immune responses. Early studies have shown that CD276 can inhibit the activation of human and mouse T cells by activating or inhibiting NFTA (nuclear factor for activated T cells), NF-KB (nuclear factor kB), and AP-1 (activator protein-1) pathways. In addition, there are results that prove that CD276 may inhibit T cell immune response by inhibiting the activity of Th1. The study by Leiner et al. also found that CD276 can down-regulate the secretion of IL-2 from T cells, thereby inhibiting the activity of T cells.
CD276 (B7-H3) as a target in tumor treatment
B7-H3 also plays a key role in a variety of tumor processes. Tumor patients with high expression of B7-H3 are often accompanied by postoperative tumor proliferation, high tumor recurrence rate, and tumor-induced death. Most studies have confirmed that B7-H3 plays a role in suppressing immune response in tumor immunity. A few studies have confirmed that B7-H3 also participates in the positive immune response to tumor cells.
① High expression of B7-H3 in tumor tissues can promote tumor occurrence and metastasis.
②B7-H3 can inhibit T cell-mediated cellular immunity, allowing tumors to escape immune surveillance.
③B7-H3 is involved in the drug resistance of tumor cells.
④B7-H3 may be involved in tumor angiogenesis.
⑤ The expression of B7-H3 is negatively correlated with tumor progression. Studies have found that patients expressing B7-H3 have a better prognosis. Loos et al. found that B7-H3 inhibits tumor progression in pancreatic cancer, which may be achieved by promoting the secretion of IFN-γ. However, in the study of gastric cancer, Arigami et al. found that patients with more expression of B7-H3 in the circulation, the more severe the pathological process of their tumors, and the worse the prognosis. And Yamato et al.'s research in pancreatic cancer showed that the high expression of B7-H3 is related to the more advanced pathological process of the tumor and lymph node metastasis. Relevant evidence shows that the relationship between tumors and B7-H3 shows a certain degree of complexity whether on different tumors or on the same tumor.