In recent years, immune checkpoint inhibitors (ICIs), particularly against PD-1/PD-L1, have revolutionized cancer treatment. However, ICI monotherapy only benefits a portion of cancer patients, while co-blockade of PD-1/PD-L1 and CTLA-4 is associated with increased IrAEs. Combined targeting of other immune checkpoints with PD-1/PD-L1 rather than CTLA-4 may be safer. B7-H3, also known as CD276, is a newer member of the same B7/CD28 superfamily as PD-1 and PD-L1. Its transcripts are ubiquitously expressed in normal tissues and solid tumors, but the protein is expressed in tumor tissues and by antigen-presenting cells, such as DC or macrophages, where it inhibits T cells and contributes to tumor immune evasion. Importantly, B7-H3 is overexpressed on a wide range of human solid cancers and correlates with negative prognosis and poor clinical outcome in patients (Wang L, et al. 2014).