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

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

PROVIDER: PRJNA495040 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7977740_1.fastq.gz	Fastqsanger.gz
	SRR7977740_2.fastq.gz	Fastqsanger.gz
	SRR7977750_1.fastq.gz	Fastqsanger.gz
	SRR7977750_2.fastq.gz	Fastqsanger.gz
	SRR7977760_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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Project description:Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy with a complex tumor ecosystem. How the interplay between tumor cells, EBV, and the microenvironment contributes to NPC progression and immune evasion remains unclear. Here we performed single-cell RNA sequencing on ~104,000 cells from 19 EBV+ NPCs and 7 nonmalignant nasopharyngeal biopsies, simultaneously profiling the transcriptomes of malignant cells, EBV, stromal and immune cells. Overall, we identified global upregulation of interferon responses in the multicellular ecosystem of NPC. Notably, an epithelial-immune dual feature of malignant cells was discovered and associated with poor prognosis. Functional experiments revealed that tumor cells with this dual feature exhibited a higher capacity for tumorigenesis. Further characterization of the cellular components of the tumor microenvironment (TME) and their interactions with tumor cells revealed that the dual feature of tumor cells was positively correlated with the expression of co-inhibitory receptors on CD8+ tumor-infiltrating T cells. In addition, tumor cells with the dual feature were found to repress IFN-γ production by T cells, demonstrating their capacity for immune suppression. Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.

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