Abstract
BACKGROUND: Single-cell transcriptomics has revolutionised our understanding of the cellular composition of the tumour microenvironment (TME) in nasopharyngeal carcinoma (NPC). Despite this progress, a key limitation of this technique has been its inability to capture epithelial/tumour cells, which has hindered further investigation of tumour heterogeneity and immune escape in NPC. METHODS: In this study, we aimed to address these limitations by analysing the transcriptomics and spatial characteristics of NPC tumour cells at single-cell resolution using scRNA/snRNA-seq and imaging mass cytometry techniques. RESULTS: Our findings demonstrate multiple patterns of immune escape mechanisms in NPC, including the loss of major histocompatibility complex (MHC) molecules in malignant cells, induction of epithelial-mesenchymal transition in fibroblast-like malignant cells and the use of hyperplastic cells in tumour nests to protect tumour cells from immune infiltration. Additionally, we identified, for the first time, a CD8+ natural killer (NK) cell cluster that is specific to the NPC TME. CONCLUSIONS: These findings provide new insights into the complexity of NPC immune landscape and may lead to novel therapeutic strategies for this disease.