Decoding the associations between cell functional states in head and neck cancer based on single-cell transcriptome

•Six cell states, including EMT, immune response, epithelial differentiation, stress, G1/S and G2/M phases were identified in HNSCC.•The association patterns between cell states were correlated with state activity.•The association pattern of EMT and immune response were correlated with immune microenvironment.•The association patterns of EMT and immune response were correlated with prognosis. Systematically identifying cancer cell functional states, especially their associations, is key to understanding the pathogenesis of cancers. Here, we systematically identified six cancer-related states, including epithelial-mesenchymal transition (EMT), immune response, epithelial differentiation, stress, G1/S and G2/M phases, in head and neck squamous cell carcinoma (HNSCC) based on single-cell RNA-sequencing (scRNA-seq). We defined the association patterns between these functional states and found the patterns were correlated with the state activity. Particularly, immune response and EMT were negatively, positively, or non-significantly correlated in samples with the highest immune response activity, the lowest activity of the two states, or with the highest EMT activity, respectively. Combining scRNA-seq data of immune cells and four independent HNSCC cohorts, we found the negative relationship between EMT and immune response was correlated with an activated immune microenvironment and a longer survival, while the non-significant relationship was correlated with an immunosuppressed microenvironment and a poor prognosis. Collectively, our results provide insight into the association patterns between functional states in HNSCC, and may facilitate the elucidation of the interactions between cancer cells and immune system during cancer progression.