Patients diagnosed with high-grade pediatric brain tumors have long-term survival rates of only 10 - 15% despite aggressive treatments with surgery and irradiation. To address this grim prognosis, cancer immunotherapy, a strategy whereby the host immune system is re-targeted/reactivated to cause tumor destruction, has recently been considered to be a potentially promising strategy. Indoleamine 2,3 dioxygenase 1 (IDO1) is an immunosuppressive enzyme that mediates the inhibition of immune cell-mediated glioblastoma (GBM) destruction. Moreover, adult GBM patients with high intratumoral IDO1 mRNA levels possess decreased overall survival. In contrast, the relevance of IDO1 remains to be explored in pediatric brain tumors. To address this knowledge gap, IDO1, in addition to other immune-modulating approaches, will be investigated in the pediatric brain tumor setting.
What are the goals of this project?
We previously showed that increased IDO1 expression is associated with decreased adult glioblastoma patient survival. We are interested in determining its relevance in malignant pediatric brain tumors.
The Children's Brain Tumor Network contributed to this project by providing access to the Pediatric Brain Tumor Atlas.
High-grade glioma/astrocytoma (WHO grade III/IV)
High-grade Gliomas (HGG) in children nearly always result in a dismal prognosis. Although novel therapeutic approaches are currently in development, preclinical testing has been limited, due to a lack of pediatric specific HGG preclinical models. These models are needed to help test the effective
Exploration of IDO1 as a therapeutic target in pediatric central nervous system tumors
Because the immune system can suppress and even eradicate tumor growth, tumor progression in central nervous system (CNS) tumors has been linked to immune evasion strategies. The capability of the immune system to recognize and inhibit the growth of cancer is dependent on its ability to recognize
Medulloblastoma, HGG, LGG, Ependymoma, DIPG
Rishi Ramesh Lulla
PDTM-10. Novel RNA-Targeting Strategy for Treating T Cell-Driven Immunosuppression in Human Diffuse Intrinsic Pontine Glioma
PURPOSE: Our laboratory’s work in adult high-grade glioma has discovered, a therapeutically-targetable pathway through the inducible expression of indoleamine 2,3 dioxygenase 1 (IDO1). IDO1 is an immunosuppressive enzyme that metabolizes tryptophan (Trp). The premise of our project is to delineat
Alicia Lenzen, Kristen Lauing, Lijie Zhai, Erik Ladomersky, Pichai Raman, Komal Rathi, Rishi Lulla, Rintaro Hashizume, Derek Wainwright