The B7-H3/CD3 immune phenotype identifies prognostic subgroups in neuroblastoma

B7-H3 is an immune checkpoint molecule implicated in tumor immune evasion and adverse prognosis in multiple malignancies. This study aimed to characterize the relationships between tumor-cell B7-H3 expression, immune-cell infiltration, clinicopathological features, and survival in malignant neuroblastic tumors, and to define an immune phenotype with potential translational relevance.

We retrospectively analyzed a population-representative cohort of 81 patients with neuroblastoma or nodular ganglioneuroblastoma diagnosed between 2009 and 2020. B7-H3 expression and CD3⁺, CD4⁺, CD8⁺, CD20⁺, and CD68⁺ immune-cell infiltration were evaluated by immunohistochemistry.

Tumors with high B7-H3 expression demonstrated reduced CD8⁺ T-cell infiltration (p = 0.045). High B7-H3 expression and low CD3⁺ T-cell infiltration were each associated with worse 60-month overall survival (OS; p = 0.025 and p = 0.014, respectively) and event-free survival (EFS; p = 0.047 and p = 0.019, respectively); however, after multivariable adjustment, only CD3⁺ T-cell infiltration retained prognostic significance. In a combined four-group model integrating these two markers, the B7-H3 low/CD3 high phenotype showed the most favorable prognosis, whereas B7-H3 high/CD3 low tumors had a 14-fold higher hazard of death (p = 0.014) and a 5.79-fold higher hazard of an EFS event (p = 0.010) compared with the favorable phenotype. Although the B7-H3/CD3 model showed only a trend toward improved OS model fit versus CD3 alone (p = 0.080), B7-H3 significantly stratified OS within the CD3-high subgroup (p = 0.019), enabling more precise identification of a particularly favorable phenotype. In a binary model, the favorable B7-H3 low/CD3 high phenotype was associated with significantly improved OS (HR = 0.095; p = 0.022) and EFS (HR = 0.219; p = 0.014) compared with all other phenotypes combined, and this effect remained significant after adjustment for age, MYCN status, and prognostic risk group.

The B7-H3 low/CD3 high immune phenotype identifies patients with markedly favorable survival in malignant neuroblastic tumors and retains a protective association after adjustment for established clinical prognostic factors. However, given the limited statistical power of the current cohort, the overall incremental prognostic value of combined B7-H3/CD3 phenotyping requires evaluation in larger, independent cohorts.