Tumor-Specific Immune Responses and Biomarkers in pediatric High-Risk Hodgkin Lymphoma Patients

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Introduction Integrating immunotherapy into pediatric classical Hodgkin lymphoma (cHL) requires understanding treatment-driven immune responses and predictive biomarkers. The Children’s Oncology Group AHOD1331 trial (NCT02166463) randomized patients (ages 2–21) with newly diagnosed high-risk cHL to receive either standard ABVE-PC chemotherapy or brentuximab vedotin (Bv)+ AVE-PC with response-adapted radiation. We evaluated peripheral blood T cell responses and soluble immune markers—including sCD30, sCD163, and TARC—in relation to event-free survival (EFS). Our goals were to (i) assess whether Bv enhanced tumor antigen-specific T cell recognition and (ii) identify potential biomarkers of treatment response. Methods Peripheral blood was collected at diagnosis and post-treatment. Plasma and PBMCs were isolated for batch testing of cytokines (Th1/Th2), sCD30, sCD163, and TARC via Luminex. T cell responses to tumor-associated antigens (PRAME, MAGEA4, survivin) were measured using IFN-γ ELISPOT after ex vivo expansion. T cell specificity was reported as spot-forming cells (SFC/10⁵ T cells). Statistical analyses included paired Wilcoxon signed-rank tests and Cox proportional hazards models. Results Among 216 patients analyzed (from 587 enrolled), 184 had paired cytokine data, 147 had sCD30/sCD163, 146 had TARC, and 71 had T cell response data. Proinflammatory cytokines (IFN-γ, IL-17a, MCP-1) significantly increased post-treatment; immunosuppressive IL-13 decreased. sCD30, sCD163, and TARC levels were significantly lower post-treatment (p<0.0001) in both arms. Lower pre-treatment sCD30 correlated with fewer EFS events across both arms with non-linear effect (Figure 2). T cell responses to PRAME significantly increased post-treatment (p=0.04). Conclusion Treatment increased T cell responses to PRAME and reduced immunosuppressive cytokines, indicating an immune environment favorable to T cell activation. Although cytokine shifts were similar across arms, our findings support further studies of immune biomarkers and tumor antigen-specific T cells to optimize immunotherapy strategies in cHL. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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