PCM-21: EXPRESSION OF IMMUNE CHECKPOINT PROTEINS IN PATIENT-DERIVED PEDIATRIC BRAIN TUMOR XENOGRAFTS

Pediatric brain tumors represent the most common solid tumor in children and the leading cause of cancer morbidity and mortality. Standard of care includes surgery, chemotherapy and radiation, which are all very damaging to a developing child. While these therapies have improved survival rates, outcomes remain extremely poor for patients with refractory disease. To improve outcomes and lessen toxicities, novel, directed therapies are needed. Recently, immunosuppressive checkpoint molecules that negatively regulate immune cell function and enable local tumor escape, such as PD-L1, CTLA-4, CD200 and Indolamine 2,3-dioxygenase (IDO), have been described in adult brain tumors. Agents designed to inhibit these proteins have shown significant efficacy in human adult solid tumor studies. Little is known about expression of these checkpoint molecules in pediatric brain tumors. After disaggregation of six patient derived xenografts (2 glioblastoma (GBM), 2 medulloblastoma (MB), and 2 supratentorial primitive neuroendocrine tumors (SPNETs)) harvested from athymic nude mice, we performed flow cytometry to quantify expression of CTLA-4, PD-L1, CD200, and IDO. All three tumor types had high expression levels of IDO (range 60.3-98.7%) and low expression of CD200 (0.5-14.4%). MB and SPNETs expressed low levels of CTLA-4 (2.2-7.5% and 4.2-11.6%, respectively) while GBM showed variable expression (20.5-38.3%). PD-L1 was highly expressed in MB (90.2-91.9%) and variably expressed in SPNETs and GBM (13.2-63.8% and 13.2-87.8%, respectively). Our results suggest that pediatric brain tumors express targetable immune checkpoint molecules, with expression of IDO consistently high, PD-L1 variable, and CD200 and CTLA-4 low.