Human natural killer cells in major histocompatibility complex class I deficiency

Patil, Neha D.; Thérésine, Maud; Zimmer, Jacques

doi:10.1111/sji.13029

Cited by 2 publications

(1 citation statement)

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“…All nucleated cells could synthesize B2M, which forms an immutable major histocompatibility complex (MHC) class I antigen small light chain subunit through non-covalent binding on the cell surface and maintain the natural conformation of MHC classI. B2M is significantly downregulated in NK-NPC and plays a role in EBV infection, which may be related to the inhibition of MHC classI antigen presentation [ 8 , 9 ]. We performed immunohistochemistry and confirmed that B2M was significantly downregulated in NK-NPC compared to the normal nasopharyngeal tissue (Fig.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2023

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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 the function of NK cell and the evolutionary trajectory of tumor cells in NK-NPC by single-cell transcriptomic analysis, proteomics and immunohistochemistry. Methods NK-NPC (n = 3) and normal nasopharyngeal mucosa cases (n = 3) were collected for proteomic analysis. Single-cell transcriptomic data of NK-NPC (n = 10) and nasopharyngeal lymphatic hyperplasia (NLH, n = 3) were obtained from Gene Expression Omnibus (GSE162025 and GSE150825). Quality control, dimension reduction and clustering were based on Seurat software (v4.0.2) process and batch effects were removed by harmony (v0.1.1) software. Normal cells of nasopharyngeal mucosa and tumor cells of NK-NPC were identified using copykat software (v1.0.8). Cell-cell interactions were explored using CellChat software (v1.4.0). Tumor cell evolutionary trajectory analysis was performed using SCORPIUS software (v1.0.8). Protein and gene function enrichment analyses were performed using clusterProfiler software (v4.2.2). Results A total of 161 differentially expressed proteins were obtained between NK-NPC (n = 3) and normal nasopharyngeal mucosa (n = 3) by proteomics (log2 fold change > 0.5 and P value < 0.05). Most of proteins associated with the nature killer cell mediated cytotoxicity pathway were downregulated in the NK-NPC group. In single cell transcriptomics, we identified three NK cell subsets (NK1-3), among which NK cell exhaustion was identified in the NK3 subset with high ZNF683 expression (a signature of tissue-resident NK cell) in NK-NPC. We demonstrated the presence of this ZNF683 + NK cell subset in NK-NPC but not in NLH. We also performed immunohistochemical experiments with TIGIT and LAG3 to confirm NK cell exhaustion in NK-NPC. Moreover, the trajectory analysis revealed that the evolutionary trajectory of NK-NPC tumor cells was associated with the status of EBV infection (active or latent). The analysis of cell-cell interactions uncovered a complex network of cellular interactions in NK-NPC. Conclusions This study revealed that the NK cell exhaustion might be induced by upregulation of inhibitory receptors on the surface of NK cells in NK-NPC. Treatments for the reversal of NK cell exhaustion may be a promising strategy for NK-NPC. Meanwhile, we identified a unique evolutionary trajectory of tumor cells with active status of EBV-infection in NK-NPC for the first time. Our study may provide new immunotherapeutic targets and new sight of evolutionary trajectory involving tumor genesis, development and metastasis in NK-NPC.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2023

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B2M overexpression correlates with malignancy and immune signatures in human gliomas

Zhang

Cui

Zhou

et al. 2021

Sci Rep

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Because of the limited treatment strategy of gliomas, the key of diagnosis and treatment is finding new molecular biomarkers. Here, we explored the potential of β2-microglobulin (B2M) to serve as a hopeful candidate for immunotherapy or diagnostic biomarker in gliomas. The genomic profiles, clinical characteristics, and immune signatures were analyzed based on TCGA and CGGA databases. We carried out the whole statistical analyses using R project. High B2M expression correlated with worse prognosis. Somatic mutations of gliomas with high B2M expression are associated with PTEN deletion and EGFR amplification. Isocitrate dehydrogenase (IDH) mutations accounted for 82% in gliomas with low B2M expression. In addition, B2M positively correlated with ESTIMATE scores, interacted with infiltrating immune and stromal cell types. B2M also suppressed anti-tumor immunity through immune related processes. Meanwhile, B2M was associated with immune checkpoint molecules and inflammatory activities. Finally, functional annotation of the identified B2M related genes verified that B2M was a potential candidate for immunotherapy. We confirmed that B2M played a critical role in tumor progression, patient prognosis and immunotherapy of gliomas.

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Human natural killer cells in major histocompatibility complex class I deficiency

Cited by 2 publications

References 9 publications

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

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

B2M overexpression correlates with malignancy and immune signatures in human gliomas

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