Larkin Brigid, Nishizaki Daisuke, Miyashita Hirotaka, Lee Suzanna, Nikanjam Mina, Eskander Ramez N, Jensen Taylor J, Pabla Sarabjot, Conroy Jeffrey M, DePietro Paul, Sicklick Jason K, Kurzrock Razelle, Kato Shumei
Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
Department of Hematology and Medical Oncology, Dartmouth Cancer Center, Lebanon, NH, USA.
Immunotargets Ther. 2025 Sep 5;14:967-977. doi: 10.2147/ITT.S534666. eCollection 2025.
Immunotherapy has transformed cancer treatment and outcomes, although resistance mechanisms remain challenging, prompting exploration of additional immune targets, including B7-H3/CD276. Indeed, B7-H3/CD276's complex and contrasting functions mark it as a jack of all trades, challenging conventional classifications of immune markers. B7-H3/CD276 is a protein belonging to the B7 family of immune regulatory molecules. It participates in immune response modulation and has been implicated in both immune activation and suppression, depending on the context though its precise immune function remains incompletely defined. B7-H3/CD276 expression is observed in various cancers and inflammatory conditions. In regard to cancer, there appears to be variability in expression both between and within malignancy types. B7-H3/CD276 targeting therapies have shown promising evidence of activity, particularly in patients over-expressing the B7-H3/CD276 protein based on immunohistochemistry. Here, we detail B7-H3/CD276's proposed immunologic and metabolic roles in the pathogenesis and progression of cancer, describe its heterogeneous patterns of RNA expression in a pan-cancer cohort, and summarize early clinical trial outcomes data.
免疫疗法已经改变了癌症治疗方式并改善了治疗结果，尽管耐药机制仍然具有挑战性，这促使人们探索包括B7-H3/CD276在内的其他免疫靶点。事实上，B7-H3/CD276复杂且相互矛盾的功能使其成为一个多面手，对免疫标志物的传统分类提出了挑战。B7-H3/CD276是一种属于B7免疫调节分子家族的蛋白质。它参与免疫反应调节，并且根据具体情况，在免疫激活和抑制中都发挥作用，尽管其确切的免疫功能仍未完全明确。在各种癌症和炎症性疾病中都观察到了B7-H3/CD276的表达。在癌症方面，不同恶性肿瘤类型之间以及同一类型内部的表达似乎都存在差异。靶向B7-H3/CD276的疗法已显示出有前景的活性证据，特别是在基于免疫组织化学检测显示B7-H3/CD276蛋白过表达的患者中。在此，我们详细阐述了B7-H3/CD276在癌症发病机制和进展中所提出的免疫和代谢作用，描述了其在泛癌队列中的RNA表达异质性模式，并总结了早期临床试验结果数据。
