Single-cell RNA sequencing defines the interplay between tumor cells, virus and microenvironment in nasopharyngeal carcinoma

Purpose: While viruses play critival roles in many human malignancies, the influence of virus infection on the tumor microenviroment(TME) and how this impacts disease progression are poorly characterized. Methods: we applied both Smart-seq2 and 10X Genomics chemistry to ~104000 cells from 19 EBV+ NPC patients and 7 nonmalignant nasopharyngeal biopsies. Results: 1. We have defined the complex interplay between tumor cells, virus infection, and the TME at single-cell resolution. 2. An epithelial-immune dual feature of malignant cells was discovered and associated with poor prognosis. 3. Stromal and immune cells in the TME were remodeled by tumor cells and virus infection. 4. EBV gene expression was found to correlate with complement factor expression in malignant cells, which, in turn, mediated T cell modulation and recruitment. 5. We subtyped NPC patients into 5 groups with different prognoses according to their respective TME compositions. Conclusion: Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.