Immunogenicity profiles in pediatric extra-cranial rhabdoid tumors: A framework for future risk stratification.

Abstract

10026 Background: Malignant rhabdoid tumors (MRTs) are highly aggressive pediatric cancers driven by SMARCB1 loss. Emerging evidence suggests that the tumor immune microenvironment may influence the biological behavior of tumors. However, data on immune patterns in extra-cranial MRTs remain extremely limited, particularly in low- and middle-income settings. This study characterizes immune marker expression and immune phenotypes in a large single-center cohort to explore their potential relevance for future risk stratification. Methods: Formalin-fixed paraffin-embedded specimens from pediatric extra-cranial MRTs were evaluated for CD4⁺, CD8⁺, and CD68⁺ immune infiltrates using immunohistochemistry. Marker expression was categorized as high or low. Tumor immune phenotypes were subsequently classified based on the balance of infiltrating populations into: (immune-cold (uniformly low), mixed (variable across markers), and inflamed (uniformly high). Associations between immune phenotypes, clinicopathologic features, and survival trends were explored to determine whether immune architecture could serve as a biologically meaningful correlate of clinical behavior. Results: Individually, none of the immune markers (CD4, CD8, CD68) showed statistically significant correlation with overall survival. However, higher CD4⁺ and CD8⁺ T-cell infiltration demonstrated a consistent trend toward improved clinical outcomes. The most informative observation emerged at the phenotype level: tumors with a mixed immune profile exhibited more favorable survival trends and delayed progression compared with immune-cold tumors, whereas fully inflamed tumors were rare. These findings suggest that the equilibrium and interaction of immune infiltrates—rather than absolute immune cell density—may shape clinical behavior. Conclusions: Pediatric extra-cranial MRTs demonstrate distinct immune microenvironment patterns that are readily identifiable using routine immunohistochemistry. Although individual immune markers did not independently predict survival, immune-cold versus mixed phenotypes reflected meaningful biological divergence and aligned with clinical outcomes. Integrating immune phenotyping into diagnostic workflows may provide a pragmatic foundation for future risk stratification and help identify patients most likely to benefit from emerging immuno-epigenetic treatment strategies. Statement of Clinical Significance: Immune profiling using routine immunohistochemistry can classify pediatric extra-cranial rhabdoid tumors into clinically relevant immune phenotypes. Identifying immune-cold versus mixed tumors may support future risk stratification and guide biologically informed treatment selection.