Microenvironment analysis of mouse and human neuroblastoma reveals shared populations and unmasks various subsets of immunosuppressive cells

High-risk neuroblastoma is a pediatric cancer with dismal prognosis. In this study, we have used various approaches including single-cell RNA sequencing to dissect the tumor microenvironment of both a transgenic mouse neuroblastoma model and a cohort of biopsies from neuroblastoma patients. From the diverse cell populations identified, our data document a striking correspondence of the microenvironment populations between tumors from both species and unravel a complex content in myeloid cells and cancer-associated fibroblasts. Within the myeloid compartment we have characterized a population of cells exhibiting features of tumor-associated neutrophils and demonstrate that these cells obtained from the mouse model have immunosuppressive properties. Altogether, our study shows that neuroblastoma tumors have an immunocompromised microenvironment characterized by dysfunctional T-cells and accumulation of immunosuppressive cells. Our data provide the rationale for novel immunotherapeutic strategies in neuroblastoma, targeting both tumor cells and components of its microenvironment. Overall design: Single-Cell RNA-seq data for MYCN-driven mouse neuroblastoma