Prognostic significance of CD8+T lymphocytes and CD68+ macrophages in assessing pathologic response in pediatric soft tissue sarcomas.

Abstract

10042 Background: The tumor immune microenvironment (TIME) plays a critical role in treatment response in pediatric oncology. Conventional clinical and demographic parameters often fail to accurately predict individual therapeutic outcomes. Increasing evidence suggests that the phenotype and spatial distribution of immune cells within the tumor may provide valuable prognostic information. This study evaluated the prognostic significance of immune markers (CD4, CD8, CD20, CD68) and their localization in predicting therapy-induced pathomorphologic response in pediatric soft tissue sarcomas (STS). Methods: A retrospective analysis was conducted in 98 pediatric patients with embryonal and alveolar STS. Immunohistochemical profiling was performed to assess the status, density, and spatial localization (intratumoral vs peritumoral) of CD4+, CD8+, CD20+, and CD68+ immune cells. Treatment response was evaluated based on the degree of therapy-induced pathomorphosis (grades I–IV) and standard imaging criteria. Statistical analysis included Spearman correlation and chi-square testing. Results: Intratumoral immune-cell infiltration demonstrated stronger prognostic value than demographic or clinical characteristics. A significant association was observed between CD8+ T-cell positivity and higher grades of pathomorphologic response (grades III–IV; p=0.001). CD68+ macrophage infiltration was also significantly correlated with tumor regression (p<0.001). Intratumoral localization of CD8+ (p=0.002) and CD68+ (p=0.021) cells was significantly associated with improved therapeutic response compared with peritumoral localization. No significant associations were identified for age (p=0.771), sex (p=0.775), or histologic subtype (p=0.960). Conclusions: Intratumoral CD8+ T lymphocytes and CD68+ macrophages are key predictors of therapeutic response in pediatric STS. These findings support the integration of immunohistochemical profiling into routine clinical practice for response stratification. The results also provide a rationale for combining standard chemotherapy with immunomodulatory strategies to enhance intratumoral immune infiltration. Clinical trial information: B2023.2.DSc/Tib856.