New frontiers in immune checkpoint B7-H3 (CD276) research and drug development

B7-H3 (CD276), a member of the B7 family of proteins, is a key player in cancer progression. This immune checkpoint molecule is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. In addition to its immune checkpoint function, B7-H3 has been linked to tumor cell proliferation, metastasis, and therapeutic resistance. Furthermore, its drastic difference in protein expression levels between normal and tumor tissues suggests that targeting B7-H3 with drugs would lead to cancer-specific toxicity, minimizing harm to healthy cells. These properties make B7-H3 a promising target for cancer therapy. Recently, important advances in B7-H3 research and drug development have been reported, and these new findings, including its involvement in cellular metabolic reprograming, cancer stem cell enrichment, senescence and obesity, have expanded our knowledge and understanding of this molecule, which is important in guiding future strategies for targeting B7-H3. In this review, we briefly discuss the biology and function of B7-H3 in cancer development. We emphasize more on the latest findings and their underlying mechanisms to reflect the new advances in B7-H3 research. In addition, we discuss the new improvements of B-H3 inhibitors in cancer drug development.