B7-H3/CD276: Novel Immune Checkpoint and Jack of All Trades

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.