Diverse Immune Responses in Different Lung Cancers Revealed via Single-Cell Sequencing
Summary
In the world, lung cancer claims the lives of about 1.796 million people each year, or 18% of all cancer-related deaths. More than 85% of lung cancer cases are non-small cell lung cancer (NSCLC), with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma as the two main subtypes (LUSC). In NSCLC, immunotherapy has consistently demonstrated clinical significance. It is challenging to predict, however, whether a specific immunotherapy will be effective for various patients due to genomic and immunogenic heterogeneity. Therefore, identifying the genomic heterogeneity among various lung cancer subtypes will aid in making more accurate treatment choices.
Research Criteria
The research idea of this article is to characterize the immune landscape in NSCLC by using single-cell RNA sequencing (scRNA-seq) techniques and to compare the differences between LUAD and LUSC subtypes. The article aims to provide an immune cellular atlas for lung cancer with a comparison between LUAD and LUSC, and to decode dynamic changes in cell percentage, heterogeneity of cell subtypes and intercellular interactions between LUAD and LUSC.
Fig.1 Experimental design. (Wang, 2022)
Sample Type
Human LUAD or LUSC samples.
Result—High-Resolution Immune Cell-Type Landscape of LUAD and LUSC Samples in Both Tumor and Corresponding Normal Tissues
The overarching aim of this present investigation was to scrutinize the immune landscape of non-small cell lung cancer (NSCLC) by subjecting tumor and adjacent normal lung specimens procured from 19 NSCLC patients (10 with lung adenocarcinoma [LUAD] and 9 with lung squamous cell carcinoma [LUSC]) to single-cell RNA sequencing (scRNA-seq) analysis. By utilizing the pan-leukocyte marker CD45, a grand total of 72,475 immune cells were identified, and subsequently segregated into nine discernable cell types, namely B cells, CD4+ T cells, CD8+ T cells, regulatory T cells, macrophages, dendritic cells, granulocytes, mast cells, and natural killer cells, via t-distributed stochastic neighbor embedding (t-SNE) dimensional reduction methodology. The proportions of immune cell types in both tumor and adjacent normal tissues exhibited marked heterogeneity among disease types, with B cells, Tregs, and mast cells constituting a greater proportion of tumor tissues, while NK cells and granulocytes being more abundant in adjacent normal tissues. Interestingly, mast cells, B cells, CD8 cells, and Tregs were predominantly derived from LUSC, whereas Mφ and DC were more dominant in LUAD. Overall, the scRNA-seq analyses conducted in this study are highly illuminating and have provided valuable insights into the immune heterogeneity of NSCLC, especially the dissimilarities between LUAD and LUSC, signifying the potential for personalized immune-based therapeutic interventions.
Fig.2 High-resolution immune cell-type landscape of LUAD and LUSC samples in both tumor and corresponding normal tissues. (Wang, 2022)
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Reference
- Wang, C.; et al. The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing. Signal Transduction and Targeted Therapy. 2022: 289.
