Neuroblastoma is the most common extracranial solid tumor in children, with around 800 new cases arising each year in the U.S. Derived from neural crest cells, the tumor is characterized by irregular peripheral nervous system cell growth at the adrenal glands or sympathetic ganglia. High-risk neuroblastoma is particularly lethal, with patients having a 50% five-year survival rate despite intensive treatment. In high-risk neuroblastoma, one cause of tumor cell proliferation is increased polyamine synthesis driven by MYCN amplification. Currently, difluoromethylornithine (DFMO) is being investigated as a potential treatment for high-risk neuroblastoma since it hinders polyamine synthesis via irreversible inhibition of ornithine decarboxylase. Since polyamines have also been shown to contribute to the immunosuppressive nature of the tumor microenvironment, we investigated the effect of DFMO on the expression of immune-related genes in neuroblastoma using a transgenic TH-MYCN+/+ murine model and digital, multiplex mRNA profiling methods.

Our results show that DFMO-treated tumors had elevated expression of genes correlating with T-cell activation and cytotoxicity— specifically those involved with antigen presentation, costimulatory signaling, and cytokine/chemokine signaling. DFMO-treated tumors also had decreased expression of gene markers for T-cell exhaustion, like CD244 and Eomes. We hope to use these results to inform future studies on combining DFMO treatment with proline and arginine depletion to produce a clinically-viable treatment for high-risk neuroblastoma.