Cell Res: Zeng Musan/Bai Fan/Zhong Xi collaborated to discover the "skin-immunity" dual characteristic tumor cells of nasopharyngeal cancer and their important biological functions.

Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with genetic, environmental and other factors, with higher incidence rates in southern China, Southeast Asia and other regions.
because the incidence of nasopharyngeal cancer in Guangdong is much higher than the national average, NPC is also known as "Guangdong cancer".
-Barr virus infection is one of the main carcinogenic factors of nasopharyngeal cancer and plays an important role in its progress.
pre-study studies were based on whole tissue or cell line samples and could not present the heterogeneity of the tumor in detail and clearly.
, in particular, there is a lack of a comprehensive and systematic understanding of the interactions between tumor cells, EBVs and tumor micro-environment (TME) cells within nasopharyngeal cancer.
In response to this scientific research, bai Fan's team of researchers from Peking University's School of Life Sciences, in collaboration with the Zengmu San/Zhongxi team at Sun Yat-sen University's Center for Cancer Prevention and Control, used the latest single-cell transcription group sequencing technique (scRNA-seq) to combine large sample genomes, transcription groups and clinical data, as well as streaming Detection, multi-immune histification, immunofluorescence, CCK-8, ELISPOT, mouse transplant tumor, cell co-culture and other experimental means, the nasopharyngeal cancer micro-environment for a comprehensive and systematic analysis of the study, and identify a unique "skin-immune" dual characteristic tumor cell subgroup.
, the study was published online in cell Research under the title: Single-cell transcriptomic analysis of the interplay between tum cells, virus, and the microenvironment in nasopharyngeal carcinoma.
In the study, the researchers first used smart-seq 2x and 10xGenomics technology platforms to capture about 104,000 single cells using tumor samples from 19 EBV-NPC patients (three of which had paired metastasis tissue) and seven non-tumor patients with nasopharyngeal tissue samples using scRNA-seq technology.
's overall experimental design and approximately 104,000 single-cell expression profiles from 26 samples were analyzed in-depth bio-informational analysis, and the researchers systematically and systematically profiled tumor cells, EBVs, mesothromats, and immune cells at the single-cell level.
same time, the researchers revealed the heterogeneity within NPC tumors at the single-cell level, as well as the potential spreading relationships of in-place and metastasis tumor tissue.
analysis of EBV gene expression map characteristics shows that the EBV incubation and lysation period genes can be expressed together in the host tumor cell.
It is worth noting that by applying a non-negative matrix factor decomposition (non-negative matrix factorization, NMF) method to tumor single-cell transcription group data, the researchers analyzed its potentially differential gene program and identified a special tumor cell-specific "epithed-immune" dual characteristic that expresses both classic epithal cell markers (such as EpiCCAM) and immunomarkers (such as MHC-II molecules, complement genes, etc.).
researchers further combined immunoglostification and bullk-RNA data analysis to confirm that tumor cells with this dual characteristic are widespread in nasopharyngeal cancer samples and are closely associated with poor clinical prognostication.
, through functional experiments such as in-body cell line and mouse transplant tumor model, the researchers revealed that tumor cells with the dual characteristics of "superseed-immunity" showed strong tumor ability.
Single-cell level found a unique "endotre-immune" subgroup of nasopharyngeal cancer tumor cells, which is widely present in nasopharyngeal cancer samples and is associated with clinically poor prognostication, and the researchers used single-cell transcription group analysis to comprehensively characterize T-cell groups, transcription status and immunoactivation/tolerance in the immunological microenvironment of nasopharyngeal tissue, as well as myelin cell groups, transcription states and developmental trajectories.
single-cell horizontal portrayal of T-cell clusters, transcriptional status and immunoactivation/tolerance in the immunologic microenvironments of nasopharyngeal cancer and non-tumor nasopharyngeal tissue by calculating IFN-alpha and IFN-yuan expression values, comparing tumor sources with With differences in IFN score for each type of cell in non-tumor source cells, the researchers found that the main cell types in the NPC tumor microenn environment had significantly higher IFN-alpha and IFN-gamma score, indicating that this global interferon response increase was prevalent in the NPC tumor microencity.
feature, which has not been reported in other tumors, may reflect the synergy between viral infection and tumor cells on tumor micro-environments.
Next, using cell-specific markers from scRNA-seq data, the researchers analyzed samples of bull RNA-seq data from 140 untreated in-place tumor tissues of nasopharyngeal cancer and divided them into five subtypes of G1-G5 based on their different expression characteristics in the tumor microenviron environment.
the clinical information of these data samples, the group analysis and comparison of their survival prognosmation relationship were carried out.
results show that the molecular forming method provides a new biomarker for clinical prognostics in NPC patients.
Single-cell data analysis explores the new nasopharyngeal cancer immuno-environment prognostic type model and tumor cells and immune micro-environment cells interoperability analysis, through single-cell tumor cell-immune micro-environment mutual analysis, the researchers unexpectedly found that the "endotred-immune" dual characteristic tumor cell subset for the immune micro-environment T cells have stronger immune suppression and regulation function.
experimental analysis confirmed that there was a positive correlation between the proportion of immersion T cells expressing co-inhibitory molecular receptors in the microenvironic environment of nasopharyngeal cancer and the tumor cells with the dual characteristics of "skin-immunity".
further co-culture experiments have found that dual-featured tumor cells have the ability to inhibit the secretion of IFN-cymbals by CD8 plus TILs, which may be an important cause of tumor immersion T cell depletion.
The dual characteristic tumor cells of "upper cortical-immunity" have obvious inhibition and regulation function for T cells, and the study presents the micro-environmental cell composition and EBV expression map of nasopharyngeal cancer tumor at the single-cell level, and analyzes the interoperability between tumor cells, EBV and TME non-tumor cells, which provides a good reference for the study of NPC.
, the study found that the "skin-immunity" dual characteristic tumor cell sub-groups, expanding the tumor cell esolysic changes in a new understanding.
It is learned that Dr. Jin Shanxuan (graduated), postdoctoral student Li Ruyan (now working at the Sanger Institute in the United Kingdom) and Li Chao (now working at the Pasteur Institute in Shanghai), Professor Chen Mingyuan of Sun Yat-sen University Cancer Prevention and Control Center, and Dr. Tang Linquan are the first authors of this paper.
Zeng Musheng, Associate Researcher of Sun Yat-sen University's Cancer Prevention and Control Center, and Bai Fan, Research Fellow of the Center for Frontier Innovation in Biomedical Sciences, Peking University, are co-authors of this paper.
Bo Zhao, Benjamin E. Gewurz of Brigham and Women's Hospital at Harvard Medical School, and Lawrence S. Young of the Warwick School of Medicine at the University of Warwick in the United Kingdom provided important guidance for this study.
the research project has also been supported by the national key research and development plan, the national science and technology major special projects, the National Natural Science Foundation of China, the Guangdong Provincial Key Research and Development Project, and the Guangdong Provincial Natural Science Foundation.
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