Characterizing the Effects of High Dose Radiation on the Neuroblastoma Tumor Microenvironment

Background:
Advanced stage neuroblastoma is frequently refractory to multimodality therapy. Immunotherapy targeting the PD-1/PD-L1 interaction has been shown to augment the host immune response following radiation therapy in mouse models of melanoma and breast carcinoma, improving local control. Neuroblastoma tumor cells also express PD-L1.

Project Goal:

We propose to: 1) characterize the host immune response in a mouse model of stereotactic body radiation therapy (SBRT) for neuroblastoma, and 2) determine whether anti-PD-1 antibody treatment potentiates this response. We will quantify circulating and tumor-infiltrating immune cell types using flow cytometry, and assess anti-tumor efficacy via contrast enhanced ultrasound. This study may provide a rationale for expanding clinical trials of anti-PD-1 reagents to encompass neuroblastoma.