Single-cell transcriptomic landscape deciphers olfactory neuroblastoma subtypes and intra-tumoral heterogeneity

Abstract Olfactory neuroblastoma (ONB) is a rare malignancy known to originate from the olfactory epithelium. The complex tumor ecosystem of this pathology remains unclear. Here we explored the cellular components within 10 ONB tumors and 1 olfactory mucosa sample based on single cell RNA profiles. We showed the intra-tumoral heterogeneity by identifying five unique expression programs among malignant epithelial cells. A novel three-classification system (Neural/Basal/Mesenchymal) of ONB was established according to the distinguished gene expression patterns. Biomarkers for categorizing bulk tumors into the new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be cautiously inferred according to the molecular features representing three tumor types,thus helping with precision chemotherapy. Herein, we also analyzed subclusters of tumor microenvironment (TME) and the interactions among different cell types in the TME. Relative abundance of immunosuppressive tumor associated macrophages indicated the benefits of immunotherapies targeting macrophages.