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The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8 +  T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8 +  T and immune-suppressive TNFRSF4 +  Treg cells in tumours might derive from peripheral CX3CR1 + CD8 +  T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3 +  DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3 +  DCs, Treg, exhausted CD8 +  T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution