Molecular functions, clinical correlates, and therapeutic prospects of B7-H3 expression in colorectal cancer: A systematic review.

Colorectal cancer (CRC) is the second leading cause of cancer-related death. The tumor immune microenvironment plays a critical role in tumor progression and immune evasion. B7-H3 (CD276), a member of the B7 family of immune checkpoint molecules, is frequently overexpressed in a variety of malignancies, including CRC. A systematic search of the literature was performed to identify studies evaluating B7-H3 in CRC.

Data were extracted on study characteristics, B7-H3 expression and detection methods, molecular and signaling pathways, and clinical outcomes. Study quality and risk of bias were assessed using the MASTER scale, and findings were synthesized using a structured narrative approach. Sixty-three studies were included. B7-H3 expression was commonly reported but demonstrated substantial variability, largely driven by differences in detection and scoring methodologies.

Preclinical evidence suggests that B7-H3 may contribute to tumor growth, invasion, immune evasion, and resistance to radio- and chemotherapy, potentially through pathways such as PI3K-AKT-mTOR, JAK-STAT, MAPK/ERK, NF-κB, VEGF/hypoxia, and Wnt/β-catenin. Preclinical studies have demonstrated that targeting B7-H3 may improve radiotherapy response and reduce metastatic burden in murine CRC models.

However, these findings should be considered preliminary and are not yet supported by clinical evidence in humans. B7-H3 targeting remains an emerging therapeutic approach that requires further clinical validation.

However, significant methodological heterogeneity in detection and scoring limits comparability across studies and precludes definitive conclusions regarding its clinical utility. B7-H3 should therefore be considered a candidate biomarker and further standardized. Prospective studies are needed to clarify its diagnostic, prognostic, and therapeutic relevance in CRC.