CD276 (B7-H3) is an immune checkpoint molecule that regulates T-cell-mediated immunity and tumor immune evasion. Functionally, CD276 suppresses anti-tumor immune responses through multiple mechanisms: it reduces natural killer (NK) cell activity 1, inhibits cytotoxic T-cell responses 2, and promotes immunosuppressive tumor microenvironments by inducing neutrophil extracellular trap (NET) formation via CXCL1-CXCR2 signaling 1. CD276 is markedly upregulated in diverse cancers including esophageal squamous cell carcinoma, head and neck cancer, triple-negative breast cancer, and brain metastases, where it correlates with poor prognosis 13. Mechanistically, mTORC1 upregulates CD276 expression through YY2 phosphorylation 2, and cancer stem cells exploit CD276 for immune escape 4. CD276 is selectively overexpressed in tumors versus normal tissues, offering tumor-specific therapeutic targeting 5. Clinically, anti-CD276 immunotherapies show promising preclinical activity through antibody-drug conjugates and checkpoint blockade, though resistance mechanisms involving ITGB6-mediated PF4+ macrophage recruitment have emerged 67. CD276 represents an emerging cancer immunotherapy target with expanding therapeutic potential across multiple solid tumor types.