11 Single-nucleus and spatially resolved multi-omics uncover intracranial germinomas’ microenvironment and associated molecular features

Abstract Introduction Germinoma is the most common intracranial germ cell tumor and has a high incidence in East Asia. It is unique in having an intense immune-cell infiltration. Method We studied the tumor microenvironment (TME) of 51 cases by snRNA-seq, spatial transcriptomics (STs) and imaging mass cytometry (IMC). Results Specific TME types were related to the interferon gene module which was inversely correlated with M2-macrophages. Macrophage migration inhibitory factor (MIF) was the main signaling pathway from tumor cells to immune cells at the peripheries of tumor regions, and we showed a spatial direction of MIF from tumor cores (immune-cold) to the tumor periphery (immune-hot), where the tumor cells expressed interferon response genes and the region was enriched with lymphocytes. We also demonstrated TME spatially and at protein level by IMC. Conclusions In this work, we showed the first detailed characterization of TME of germinomas at single-nucleus and spatial resolution, and contributed clues for potential immunotherapy