Comprehensive single-cell transcriptomic and proteomic analysis reveals NK cell exhaustion and unique tumor cell evolutionary trajectory in non-keratinizing nasopharyngeal carcinoma

• DOI: 10.1186/s12967-023-04112-8
• Publication Date: 2023-04-25T11:11:26Z
• Authors: Cuimin Chen; Chun Wang; Ruifang Pang; Huanyu Liu; Weihua Yin; Jiakang Chen; Lili Tao
• Keywords: Proteomics; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Nasopharyngeal Carcinoma; Squamous Cell Carcinoma of Head and Neck; Research; R; Nasopharyngeal Neoplasms; single-cell RNA sequencing; 3. Good health; NK cell exhaustion; Killer Cells, Natural; EBV; Head and Neck Neoplasms; Evolutionary trajectory; Medicine; Humans; Transcriptome; NK-NPC

Abstract Background Nonkeratinizing nasopharyngeal carcinoma (NK-NPC) has a strong association with Epstein-Barr virus (EBV) infection. The role of NK cells and the tumor cell evolutionary trajectory in NK-NPC remain unclear. In this study, we aim to investigate function by single-cell transcriptomic analysis, proteomics immunohistochemistry. Methods (n = 3) normal mucosa cases were collected for proteomic analysis. Single-cell data 10) lymphatic hyperplasia (NLH, n obtained from Gene Expression Omnibus (GSE162025 GSE150825). Quality control, dimension reduction clustering based on Seurat software (v4.0.2) process batch effects removed harmony (v0.1.1) software. Normal identified using copykat (v1.0.8). Cell-cell interactions explored CellChat (v1.4.0). Tumor analysis was performed SCORPIUS Protein gene enrichment analyses clusterProfiler (v4.2.2). Results A total 161 differentially expressed proteins between (log 2 fold change > 0.5 P value < 0.05). Most associated nature killer mediated cytotoxicity pathway downregulated group. single transcriptomics, three subsets (NK1-3), among which exhaustion NK3 subset high ZNF683 expression (a signature tissue-resident cell) NK-NPC. We demonstrated presence + but not NLH. also immunohistochemical experiments TIGIT LAG3 confirm Moreover, revealed that status EBV infection (active or latent). cell-cell uncovered complex network cellular Conclusions This study might be induced upregulation inhibitory receptors surface Treatments reversal may promising strategy Meanwhile, unique active EBV-infection first time. Our provide new immunotherapeutic targets sight involving genesis, development metastasis