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- W2547521206 abstract "Purpose: Indoleamine 2,3 dioxygenase 1 (IDO1) and tryptophan dioxygenase (TDO2) are tryptophan catabolic enzymes that have been implicated in facilitating immunosuppression in cancer. With respect to the central nervous system (CNS), both enzymes have been correlated with decreased overall survival in adult patients with glioma. Based on these observations, we questioned whether pediatric CNS tumors, which constitute the most common form of solid cancer in children, also possess expression and activity for these immunosuppressive mediators. Experimental Design: Purified RNA from pediatric patient tumor tissue was obtained from the Children9s Brain Tumor Tissue Consortium (Philadelphia, PA) and utilized for qRT-PCR analysis of IDO1, TDO2, CD3e, IFNγ, and TGFβ1. Primary cell lines were propagated from fresh tumor tissue acquired by Dr. Rintaro Hashizume, Ph.D. (Northwestern University) and cultured for 48 hours alone or with a combination of 100 ng/mL IFNγ and 10, 50, 250 or 1000 nM L1MT, D1MT and BGB-5777; a novel pharmaceutical-grade IDO1 inhibitor (Beigene). Cell culture supernatants were collected at 48 hours for detection of tryptophan (Trp) and kynurenine (Kyn) levels by high pressure liquid chromatography. The cells were collected confirmed for IDO1 protein expression via western blot. Results: RT-PCR defined two populations of pediatric high grade glioma (HGG) based on high (>3 fold expression compared to average) versus low ( Conclusion: These data show for the first time that, IDO1 is expressed in pediatric tumors and the novel blood brain barrier-penetrating IDO1 inhibitor, BGB-5777, is a highly potent inhibitor of enzymatic activity in this setting. Given that IDO1 inhibitors are already in multiple clinical trials for adults with brain cancer, these data suggest that BGB-5777 may be a valuable tool for inhibiting IDO1 in the setting of malignant pediatric brain cancer. Citation Format: Kristen Lauing, Rishi Lulla, Lijie Zhai, Rintaro Hashizume, Jason Fangusaro, Derek A. Wainwright. Characterization of IDO1 and TDO2 in pediatric central nervous system tumors [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A051." @default.
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- W2547521206 date "2016-10-31" @default.
- W2547521206 modified "2023-09-27" @default.
- W2547521206 title "Abstract A051: Characterization of IDO1 and TDO2 in pediatric central nervous system tumors" @default.
- W2547521206 doi "https://doi.org/10.1158/2326-6066.imm2016-a051" @default.
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