Multiregional single-cell transcriptomics reveals an association between partial EMT and immunosuppressive states in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and metastatic, and the mechanisms driving OSCC development, progression, and metastasis remain elusive. Here, we performed single-cell RNA sequencing on 231,442 cells obtained from the tumor core (TC), tumor periphery (TP), adjacent surrounding tissue (ST), and metastatic lymph node (mLN) samples of 10 patients with human papillomavirus (HPV)-negative OSCC. TP and TC showed no major immune cell phenotype differences. Interestingly, partial EMT (p-EMT) cells showed significant activation of glycolysis and hypoxia signatures, serving as potential biomarkers for clinical outcomes. Moreover, p-EMT scores of epithelial cells positively correlated with M2 scores of tumor-associated macrophages, while the proportion of p-EMT at TP was negatively associated with that of GZMB (+) exhausted CD8(+) T cells with cytotoxic potential and TNFRSF9 (+) mast cells, conferring an adverse prognosis. Our study provides insights into understanding the interplay between intratumoral heterogeneity and the tumor microenvironment of advanced HPV-negative OSCC.