Aberrant indoleamine 2,3 dioxygenase (IDO) expression is present in pediatric patients with Hodgkin's lymphoma

Abstract

9531 Background: Indoleamine 2,3 dioxygenase (IDO) is a tryptophan-catabolizing enzyme capable of inducing local immunosuppression and systemic tolerance. IDO activity, as measured by serum levels of tryptophan (TRP) and kynurenine (KYN), has been shown to portend a worse prognosis in several different malignancies. Additionally, IDO expression in tumor draining lymph nodes predicts a worst outcome in patients with malignant melanoma making IDO a potential target for therapeutic intervention. To date, no studies have evaluated the expression pattern of IDO in the setting of pediatric Hodgkin Disease. Methods: 20 cases of pediatric Hodgkin Disease (2 stage I, 11 stage II, 2 stage III and 5 stage IV), treated on Children's Oncology Group trials were studied. Paraffin-embedded tumor tissues and matching pre- and post-chemotherapy sera were obtained via the Cooperative Human Tissue Network (CHTN). Immunohistochemical studies were performed on sections of paraffin-embedded tissues to evaluate aberrant IDO expression and secondary serum KYN/TRP changes were analyzed. Results: Tumor tissues from 17/20 patients (85%) were positive for IDO. Two cases showed no expression and one was not evaluable due to tissue necrosis. Morphologically several cell types were noted to express IDO including eosinophils, dendritic cells and large cells, some of which are bi-nucleated, possibly consistent with Reed-Sternberg cells and variants. The mean serum KYN/TRP ratio was elevated pre-chemotherapy in comparison to post therapy levels (P value=0.0043 by Wilcoxon sign rank test). Conclusions: This pilot data demonstrates that aberrant IDO expression is a common finding in pediatric Hodgkin Disease, and that the potential immunomodulatory role of IDO expression in the context of Hodgkin Disease needs to be further studied. These data warrant further prospective evaluation in a larger cohort of patients to determine the clinical applicability of this observation. No significant financial relationships to disclose.