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British Journal of Cancer www.nature.com/bjcREVIEW ARTICLE OPENMolecular DiagnosticsMapping B7-H3 in the tumour microenvironment: a systematicreview of stromal, vascular and immune expressionLaura Privitera1,2,5 , Piero Alberti 1,2,5 , Simone Oliver Senica 1 , Jonathan J. Neville 1,2 , Judith Wienke 3 , John Anderson 1andStefano Giuliani1,2,4 ?© Crown 2026B7 homologue 3 (B7-H3) is a promising therapeutic target in oncology. While its expression on tumour cells is well established, itsdistribution and role within the tumour microenvironment (TME) remain less clearly def i ned. This review systematically evaluatesB7-H3 protein expression across human TME compartments and explores reported associations with tumour progression andclinical outcomes. A comprehensive literature search was conducted up to June 2025, identifying studies that assessed andquantif i ed B7-H3 expression in the TME of solid human tumours. Thirty-one studies met the inclusion criteria. B7-H3 expression wasfrequently reported in tumour-associated vasculature, where higher levels have been reported to associate with aggressivehistopathological features and reduced survival. Stromal expression, predominantly in cancer-associated f i broblasts, was identif i edin over half of the tumour types studied and was associated with immune evasion and stromal remodelling gene signatures,although f i ndings 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 f i ndings identify tumour vasculature and myeloid-derived cells as B7-H3-positive compartments within the TME, although their clinical and therapeutic relevance requires further validation. PROSPEROregistration number: CRD420251129792British Journal of Cancer; https://doi.org/10.1038/s41416-026-03573-0BACKGROUNDThe tumour ecosystem comprises more than just cancer cells. It is acomplex environment where cancer cells interact with cellularcomponents, as well as tumour extracellular matrix (ECM) andsoluble factors that collectively create the tumour microenviron-ment(TME).TheTMEcreatesadynamicnichethatpromotestumoursurvival, progression and metastasis, as well as immune evasion andresistance to anti-cancer therapies [1, 2]. Key cellular components ofthe TME include stromal cells such as cancer-associated f i broblasts(CAFs), immune cells including neutrophils, dendritic cells (DCs),inf i ltrating lymphocytes and tumour-associated macrophages(TAMs), as well as tumour-associated endothelial cells (ECs) andvascular smooth muscle cells (VSMCs) [3]. (Fig. 1).B7 homologue 3 (B7-H3), also known as CD276, is a member ofthe B7 family of immune checkpoint molecules. It is overexpressedin many human cancers and is emerging as a key mediator ofimmune and non-immune processes in tumours [4]. Initiallydescribed as a costimulatory molecule boosting T-cell activationand interferon-γ production when induced on dendritic cells andmonocytes by inf l ammatory stimuli, it was later identif i ed as atumour-associated antigen capable of shielding tumour cells fromnatural killer cell-mediated lysis [5, 6]. B7-H3, is a type Itransmembrane glycoprotein with two isoforms: 2IgB7-H3 and4IgB7-H3 [7]. Mouse B7-H3 consists entirely of 2Ig isoforms. Initialinsights into its function were obtained from crosses between B7-H3 knock-out mice and genetically engineered mouse models forautoimmune diseases, which together suggested that the mouse2Ig isoform has an immunostimulatory role [8]. In contrast, thepredominant isoform in humans is the 4IgB7-H3, and availableevidence points to its role being in immune suppression [9, 10].B7-H3 lacks a known intracellular signalling motif, suggesting itsfunctions may be mediated via interactions with externalreceptors [11]. However, despite extensive research, the specif i creceptors for B7-H3 in mouse and human remain unknown [12].B7-H3 has become a promising therapeutic target in oncology,with various strategies currently being explored, including mono-clonal antibodies, antibody–drug conjugates and chimeric antigenreceptor (CAR) T-cell therapies [9, 13–16]. However, the success ofthese approaches depends not only on the tumour cells but also onthe non-malignant components of the TME. Extensive evidence1 Cancer Section, Developmental Biology and Cancer Programme, University College London, Great Ormond Street Institute of Child Health, London, UK. 2 Department ofSpecialist Neonatal and Paediatric Surgery, Great Ormond Street Hospital for Children NHS Trust, London, UK.3 Princess Máxima Centre for Paediatric Oncology, Utrecht, TheNetherlands.4 UCL Hakwes Institute, University College London, London, UK. 5 These authors contributed equally: Laura Privitera, Piero Alberti.? email: stefano.giuliani@gosh.nhs.uk; s.giuliani@ucl.ac.ukReceived: 30 December 2025 Revised: 2 July 2026 Accepted: 24 July 20261234567890();,: