Dataset Information

Single-cell analysis reveals the multiple patterns of immune escape in the nasopharyngeal carcinoma microenvironment.

ABSTRACT:

Background

Single-cell transcriptomics has revolutionised our understanding of the cellular composition of the tumour microenvironment (TME) in nasopharyngeal carcinoma (NPC). Despite this progress, a key limitation of this technique has been its inability to capture epithelial/tumour cells, which has hindered further investigation of tumour heterogeneity and immune escape in NPC.

Methods

In this study, we aimed to address these limitations by analysing the transcriptomics and spatial characteristics of NPC tumour cells at single-cell resolution using scRNA/snRNA-seq and imaging mass cytometry techniques.

Results

Our findings demonstrate multiple patterns of immune escape mechanisms in NPC, including the loss of major histocompatibility complex (MHC) molecules in malignant cells, induction of epithelial-mesenchymal transition in fibroblast-like malignant cells and the use of hyperplastic cells in tumour nests to protect tumour cells from immune infiltration. Additionally, we identified, for the first time, a CD8+ natural killer (NK) cell cluster that is specific to the NPC TME.

Conclusions

These findings provide new insights into the complexity of NPC immune landscape and may lead to novel therapeutic strategies for this disease.

SUBMITTER: Lin Q

PROVIDER: S-EPMC10288070 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Single-cell analysis reveals the multiple patterns of immune escape in the nasopharyngeal carcinoma microenvironment.

Lin Qianyu Q Zhou Yaqi Y Ma Jie J Han Sanyang S Huang Yunchuanxiang Y Wu Feng F Wang Xuejuan X Zhang Yanan Y Mei Xueshuang X Ma Lan L

Clinical and translational medicine 20230601 6

<h4>Background</h4>Single-cell transcriptomics has revolutionised our understanding of the cellular composition of the tumour microenvironment (TME) in nasopharyngeal carcinoma (NPC). Despite this progress, a key limitation of this technique has been its inability to capture epithelial/tumour cells, which has hindered further investigation of tumour heterogeneity and immune escape in NPC.<h4>Methods</h4>In this study, we aimed to address these limitations by analysing the transcriptomics and spa ...[more]

PMID: 37349991

Similar Datasets

Project description:BackgroundCombinatory therapeutic strategy containing immunochemotherapy as part of induction therapy components is one of the current trends in the treatment of high-risk metastatic locally advanced nasopharyngeal carcinoma (NPC). However, the mechanism underlying the heterogeneity of response at the single-cell level has not been underexplored.Methods18 bulks and 11 single-cell RNA sequencing from paired before-treatment and on-treatment samples in patients with treatment-naive high-risk metastatic locally advanced NPCs were obtained. Following quality control, a total of 87 191 cells were included in the subsequence bioinformatics analysis.ResultsImmunochemotherapy was associated with on-treatment tumour microenvironment (TME) remodelling, including upregulation of anti-TMEs signatures, downregulation of pro-TMEs signatures, reversing CD8+ T exhaustion, and repolarizing proinflammatory TAMs. For the patients achieving a complete response, the cytotoxic activity of CD8+ T cells was stimulated and more interferon-gamma was provided, which would be the key for TAMs proinflammatory repolarization and eventually promote the CD8+ T cells maturation in turn. Among patients who did not reach complete response, differentiation and hypoxia signatures for endothelial cells were elevated after therapy. These patients exhibited higher levels of immune checkpoint genes in malignant cells at the baseline (before treatment), and decreased tumour antigen presentation activity, which may underlie the resistance mechanism to therapy.ConclusionsThis study pictures a map of TME modulation following immunochemotherapy-based combination induction therapy and provides potential future approaches.HighlightsImmunochemotherapy remodeled T cell phenotypes. For the patients achieving complete response, more interferon gamma was provided by CD8+ T cells after therapy, which would be the key for TAMs pro-inflammatory repolarization and eventually promote the CD8+ T cells maturation in turns. Among patients who did not reach complete response, malignant cells exhibited higher level of immune checkpoint genes before therapy, and decreased tumor antigen presentation activity, which may underlie the resistance mechanism to therapy.

Dataset Information

Single-cell analysis reveals the multiple patterns of immune escape in the nasopharyngeal carcinoma microenvironment.

Background

Methods

Results

Conclusions

Publications

Single-cell analysis reveals the multiple patterns of immune escape in the nasopharyngeal carcinoma microenvironment.

Similar Datasets

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