Mapping B7-H3 in the tumour microenvironment: a systematic review of stromal, vascular and immune expression

B7 homologue 3 (B7-H3) is a promising therapeutic target in oncology. While its expression on tumour cells is well established, its distribution and role within the tumour microenvironment (TME) remain less clearly defined. This review systematically evaluates B7-H3 protein expression across human TME compartments and explores reported associations with tumour progression and clinical outcomes. A comprehensive literature search was conducted up to June 2025, identifying studies that assessed and quantified B7-H3 expression in the TME of solid human tumours. Thirty-one studies met the inclusion criteria. B7-H3 expression was frequently reported in tumour-associated vasculature, where higher levels have been reported to associate with aggressive histopathological features and reduced survival. Stromal expression, predominantly in cancer-associated fibroblasts, was identified in over half of the tumour types studied and was associated with immune evasion and stromal remodelling gene signatures, although findings varied across studies. Within the immune compartment, B7-H3 was most abundantly expressed in myeloid-derived suppressor cells, macrophages, and dendritic cells, and has been reported to associate to immunosuppressive phenotypes, advanced disease stage and poorer clinical outcomes. These findings identify tumour vasculature and myeloid-derived cells as B7-H3-positive compartments within the TME, although their clinical and therapeutic relevance requires further validation. PROSPERO registration number: CRD420251129792.