Single-Cell Spatial Proteomics Analyses of Head and Neck Squamous Cell Carcinoma Reveal Tumor Heterogeneity and Immune Architectures Associated with Clinical Outcome

Recent research has provided compelling evidence that the spatial organization of cells within the tumor-immune microenvironment (TiME) of solid tumors correlates with survival and response to therapy in numerous cancer types. Here, we report results of a quantitative single-cell spatial analysis of the TiME of primary and recurrent human head and neck squamous cell carcinoma (HNSCC) tumors, that builds upon our initial longitudinal study of these same HNSCCs that annotated immune complexity at near single cell resolution. Herein, we extended multiple spatial algorithms to quantify spatial landscapes of immune cells within TiMEs. Most notably, we report that spatial compartmentalization, rather than mixing, between neoplastic tumor cells and immune cells is associated with longer patient survival, as well as revealing mesenchymal spatial cellular neighborhoods and their association with improved patient outcomes. Results reported herein are concordant with studies in other tumor types, thus indicating that cellular heterogeneity within tumors trends with spatial TiME features, and are likely prognostic for patient survival.