IMMU-01. CYTOTOXIC AND SUPPRESSIVE IMMUNE CELL TRAFFICKING TO PEDIATRIC BRAIN TUMORS: A BALANCING ACT

BACKGROUND: Because of the potential to specifically eliminate tumor cells while leaving healthy tissue intact, immunotherapy is a particularly appealing treatment option for children with brain tumors. However, little is known about the tumor microenvironment (TME) in pediatric brain tumors, and its effect on the immune system is unclear. We have previously shown that in contrast to adult glioblastoma (GBM), which have extensive accumulation of a variety of suppressive immune cells, such as tumor-associated macrophages (TAMs), aggressive pediatric brain tumors such as medulloblastomas and high grade gliomas (HGG) do not have a similar accumulation of immune cells in the TME. We hypothesize that pediatric brain tumors escape recognition by the immune system as a result of defects in immune trafficking to the TME and/or failure to recognize the tumor. METHODS: Quantitative PCR for immunosuppressive factors was performed on pediatric brain tissue (non-tumor brain, pilocytic astrocytoma, or GBM, n=5 per group). Chemokine concentration in plasma (n=77) obtained at the time of diagnosis or during follow-up treatment was measured by bioplex analysis. Surface protein expression on patient leukocytes (n=40) was evaluated by flow cytometry. RESULTS: Pediatric brain tumors do not exhibit high levels of immunosuppressive factors such as PD-L1 or M-CSF relative to normal brain. Plasma samples from pediatric brain tumor patients have decreased concentrations of chemokines that attract suppressive immune cells to the tumor site relative to control patients without tumor. Furthermore, we did not observe a change in chemokines that attract cytotoxic T and NK cells, supporting the hypothesis that immune cell trafficking and routine surveillance of transformed cells may be impaired in an immature immune system. CONCLUSIONS: These data suggest that in pediatric patients, designing cell therapy products that educate cytotoxic effectors and improve their homing to tumor may be more important than overcoming immunosuppression in the TME.