Dataset Information

TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment.

ABSTRACT: Cancer immunotherapy targeting co-inhibitory pathways by checkpoint blockade shows remarkable efficacy in a variety of cancer types. However, only a minority of patients respond to treatment due to the stochastic heterogeneity of tumor microenvironment (TME). Recent advances in single-cell RNA-seq technologies enabled comprehensive characterization of the immune system heterogeneity in tumors but posed computational challenges on integrating and utilizing the massive published datasets to inform immunotherapy. Here, we present Tumor Immune Single Cell Hub (TISCH, http://tisch.comp-genomics.org), a large-scale curated database that integrates single-cell transcriptomic profiles of nearly 2 million cells from 76 high-quality tumor datasets across 27 cancer types. All the data were uniformly processed with a standardized workflow, including quality control, batch effect removal, clustering, cell-type annotation, malignant cell classification, differential expression analysis and functional enrichment analysis. TISCH provides interactive gene expression visualization across multiple datasets at the single-cell level or cluster level, allowing systematic comparison between different cell-types, patients, tissue origins, treatment and response groups, and even different cancer-types. In summary, TISCH provides a user-friendly interface for systematically visualizing, searching and downloading gene expression atlas in the TME from multiple cancer types, enabling fast, flexible and comprehensive exploration of the TME.

SUBMITTER: Sun D

PROVIDER: S-EPMC7778907 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment.

Sun Dongqing D Wang Jin J Han Ya Y Dong Xin X Ge Jun J Zheng Rongbin R Shi Xiaoying X Wang Binbin B Li Ziyi Z Ren Pengfei P Sun Liangdong L Yan Yilv Y Zhang Peng P Zhang Fan F Li Taiwen T Wang Chenfei C

Nucleic acids research 20210101 D1

Cancer immunotherapy targeting co-inhibitory pathways by checkpoint blockade shows remarkable efficacy in a variety of cancer types. However, only a minority of patients respond to treatment due to the stochastic heterogeneity of tumor microenvironment (TME). Recent advances in single-cell RNA-seq technologies enabled comprehensive characterization of the immune system heterogeneity in tumors but posed computational challenges on integrating and utilizing the massive published datasets to inform ...[more]

PMID: 33179754

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Project description:Highlights • Tregs lead immune-evasive TME of early lung cancer of never smoker.• Depletion of γδT and NK cells and infiltration of B cells begins in early TME.• Early lung cancer cells were characterized by dysregulated surfactant pathway.• CAFs show enrichment of gene sets that inhibit vascular formation. In tumor tissue, tip-like endothelial cells begin to be replaced with immature ones. With the increasing interest in health screening with chest CT Ground-glass nodule (GGN) has become one of the common lung lesions encountered in daily medical practice. Because lung adenocarcinoma in the form of GGN is an ideal model for studying early lung carcinogenesis, 11 GGN and normal lung specimens from 6 never smoker patients were studied by single-cell RNA sequencing. Lung cancer cells showed enrichment of gene sets related to small vesicle processing and surfactant homeostasis compared to non-malignant lung epithelial cells, suggesting the dysregulation of surfactant pathway may be involved in early lung carcinogenesis. Along with cancer-associated fibroblasts showing enrichment of gene sets involved in negative regulation of protein kinase activity and negative regulation of endothelial cell proliferation, tumor microenvironment (TME) was dominated by infiltration of TNFRSF4+/TNFRSF18+/CTLA4+ regulatory T cells (Treg) and depletion of CD8+ cytotoxic T cells (TC) and γδTC. Majority of mucosa-associated lymphoid tissue B cells (BCs) and follicular BCs were detected within tumor tissue, which was associated with CXCL13 overexpressed in intratumoral Tregs and CD4+ memory TCs. Coordination of components of the TME towards immune evasion is governed by Tregs from the onset of lung cancer, requiring unremitting efforts to target and overcome them. This provision of information on changes in cancer cell-specific biomarkers and TME using early lung cancer from never smokers will provide new insight into early lung carcinogenesis and useful targets for treatment.

Dataset Information

TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment.

Publications

TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment.

Similar Datasets

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