Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules

Lu, Tao; Yang, Xiaodong; Shi, Yu; Zhao, Mengnan; Bi, Guoshu; Liang, Jiaqi; Chen, Zhencong; Huang, Yiwei; Jiang, Wei; Zhang, Lin; Xi, Junjie; Wang, Shuai; Yang, Yong; Zhan, Cheng; Wang, Qun; Tan, Liang

doi:10.1038/s41421-020-00200-x

Cited by 71 publications

(75 citation statements)

References 52 publications

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“…Second, capillary ECs in healthy lung expressed a gene signature of semi-professional antigen-presenting cells, but these immunomodulatory ECs are underrepresented in lung tumors [ 6 ]. In agreement, genes related to antigen presentation and chemotaxis were downregulated in TECs from SADC compared to early-stage GGN-ADC [ 83 ]. On the other hand, ECs with transcriptomic features of high endothelial venules (HEVs) were more abundant in tumors [ 84 ], suggesting a complex regulation of tumor immunity by TECs.…”

Section: Ec Heterogeneity In Cancermentioning

confidence: 63%

“…Surprisingly, genes involved in antigen presentation (MHC class I and II), chemotaxis ( CCL2 , CCL18 , IL6 ), and immune cell homing ( ICAM1 ) were downregulated in TECs compared to normal lung ECs, raising the question whether TECs potentially contribute to immune tolerance [ 81 ]. In agreement, compared to early-stage ground glass nodules adenocarcinoma (GGN-ADC), TECs from late-stage solid adenocarcinoma (SADC) exhibited lower levels of genes involved in antigen presentation and chemotaxis [ 83 ].…”

Section: Ec Heterogeneity In Cancermentioning

confidence: 88%

“…To name a few, genes involved in lipid metabolism are upregulated in capillary TECs, while venous TECs exhibit an increased prostaglandin metabolic transcriptome signature [ 31 ]. Further, compared to early-stage GGN-ADC, TECs from late-stage SADC are enriched in metabolic processes [ 83 ]. Comparative single-cell analysis of three distinct cancer types (colorectal, lung, ovarian) revealed upregulation of genes involved in glycolysis and OXPHOS in tip cells [ 84 ].…”

Section: The Role Of Metabolism In Ec Plasticity and Heterogeneitymentioning

confidence: 99%

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Endothelial cell plasticity at the single-cell level

et al. 2021

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The vascular endothelium is characterized by a remarkable level of plasticity, which is the driving force not only of physiological repair/remodeling of adult tissues but also of pathological angiogenesis. The resulting heterogeneity of endothelial cells (ECs) makes targeting the endothelium challenging, no less because many EC phenotypes are yet to be identified and functionally inventorized. Efforts to map the vasculature at the single-cell level have been instrumental to capture the diversity of EC types and states at a remarkable depth in both normal and pathological states. Here, we discuss new EC subtypes and functions emerging from recent single-cell studies in health and disease. Interestingly, such studies revealed distinct metabolic gene signatures in different EC phenotypes, which deserve further consideration for therapy. We highlight how this metabolic targeting strategy could potentially be used to promote (for tissue repair) or block (in tumor) angiogenesis in a tissue or even vascular bed-specific manner.

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Section: Ec Heterogeneity In Cancermentioning

confidence: 63%

Section: Ec Heterogeneity In Cancermentioning

confidence: 88%

Section: The Role Of Metabolism In Ec Plasticity and Heterogeneitymentioning

confidence: 99%

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Endothelial cell plasticity at the single-cell level

et al. 2021

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“…We further investigated how Tns1 high fibroblasts interacted with CD8 + T cell in the TME based on aforementioned single-cell RNA sequencing data of mouse esophageal cancer model. We classified CD8 + T cells into 6 clusters (Supplementary Figure 12A) , including four clusters of naive T cells (Tn), one cluster of cytotoxic T cell (Ct), and one cluster of exhausted T cell (Ex) according to canonical markers (Supplementary Figure 12B) [ 49 , 67 , 68 ]. Then, we used CellChat to infer the cell-cell communication network among CD8 + T cells and Tns1 high fibroblasts [52] .…”

Section: Resultsmentioning

confidence: 99%

Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

Chen

et al. 2021

EBioMedicine

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Background Esophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics. Methods Expression profiles of multiple ESCC datasets were integrated. ATAC-seq and RNA-seq were combined to reveal the chromatin accessibility features. A prognosis-related subtype classifier (PrSC) was constructed, and its association with the tumor microenvironment (TME) and immunotherapy was assessed. The key gene signature was validated in clinical samples. Based on the TME heterogeneity of ESCC patients, potential subtype-specific therapeutic agents were screened. Findings The common differentially expressed genes (cDEGs) in ESCC were identified. Up-regulated genes (HEATR1, TIMELESS, DTL, GINS1, RUVBL1, and ECT2) were found highly important in ESCC cell survival. The expression alterations of PRIM2, HPGD, NELL2, and TFAP2B were associated with chromatin accessibility changes. PrSC was a robust scoring tool that was not only associated with the prognosis of ESCC patients, but also could reflect the TME heterogeneity. TNS1 high fibroblasts were associated with immune exclusion. TG-101348 and Vinorelbine were identified as potential subtype-specific therapeutic agents. Besides, the application of PrSC into two immunotherapy cohorts indicated its potential value in assessing treatment response to immunotherapy. Interpretation Our study depicted the multi-dimensional characterization of ESCC, established a robust scoring tool for the prognosis assessment, highlighted the role of TNS1 high fibroblasts in TME, and identified potential drugs for clinical use. Funding A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

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“…As a kind of important tumor-infiltrating lymphocytes (TILs), low-expressed NK cells are discovered on multiple cancers, which are linked with a poor prognosis of patients, too ( 42 , 43 ). A single cell sequencing study of lung GGO and solid nodules concluded that NK cell cytotoxicity was lower in solid nodules, which showed that the function of the NK cell decreased during the progression of lung adenocarcinoma ( 44 ). Mechanism researches also indicate the functional improvement of NK cells may induce tumor regression ( 36 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity

Zhang¹,

He²,

Cai³

et al. 2021

Front. Oncol.

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BackgroundLung ground-glass opacities (GGOs) are an early manifestation of lung adenocarcinoma. It is of great value to study the changes in the immune microenvironment of GGO to elucidate the occurrence and evolution of early lung adenocarcinoma. Although the changes of IL-6 and NK cells in lung adenocarcinoma have caught global attention, we have little appreciation for how IL-6 and NK cells in the lung GGO affect the progression of early lung adenocarcinoma.MethodsWe analyzed the RNA sequencing data of surgical specimens from 21 patients with GGO-featured primary lung adenocarcinoma and verified the changes in the expression of IL-6 and other important immune molecules in the TCGA and GEO databases. Next, we used flow cytometry to detect the protein expression levels of important Th1/Th2 cytokines in GGO and normal lung tissues and the changes in the composition ratio of tumor infiltrating lymphocytes (TILs). Then, we analyzed the effect of IL-6 on NK cells through organoid culture and immunofluorescence. Finally, we explored the changes of related molecules and pathway might be involved.ResultsIL-6 may play an important role in the tumor microenvironment of early lung adenocarcinoma. Further research confirmed that the decrease of IL-6 in GGO tissue is consistent with the changes in NK cells, and there seems to be a correlation between these two phenomena.ConclusionThe IL-6 expression status and NK cell levels of early lung adenocarcinoma as GGO are significantly reduced, and the stimulation of IL-6 can up-regulate or activate NK cells in GGO, providing new insights into the diagnosis and pathogenesis of early lung cancer.

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Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules

Cited by 71 publications

References 52 publications

Endothelial cell plasticity at the single-cell level

Endothelial cell plasticity at the single-cell level

Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity

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