The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 374 - 403

Published: March 1, 2023

Language: Английский

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Cancer-associated fibroblasts in the single-cell era

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(7), P. 793 - 807

Published: July 26, 2022

Language: Английский

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Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 4, 2022

Abstract Cancer-associated fibroblasts (CAFs) are the predominant components of tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different types. Here, we perform pan-cancer analysis 226 samples 10 solid types to profile TME at single-cell resolution, illustrating commonalities/plasticity heterogenous CAFs. Activation trajectory major CAF is divided into three states, exhibiting distinct interactions with other cell components, relating prognosis immunotherapy. Moreover, minor represent alternative origin from (e.g., endothelia macrophages). Particularly, presentation endothelial-to-mesenchymal transition CAF, which may interact proximal SPP 1 + tumor-associated macrophages, implicated in survival stratifications. Our study comprehensively profiles shared dynamics CAFs, highlight heterogeneity plasticity Browser integrated information available https://gist-fgl.github.io/sc-caf-atlas/ .

Language: Английский

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Single-cell spatial landscapes of the lung tumour immune microenvironment

Nature, Journal Year: 2023, Volume and Issue: 614(7948), P. 548 - 554

Published: Feb. 1, 2023

Abstract Single-cell technologies have revealed the complexity of tumour immune microenvironment with unparalleled resolution 1–9 . Most clinical strategies rely on histopathological stratification subtypes, yet spatial context single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize and immunological landscape samples from 416 patients lung adenocarcinoma across five histological patterns. We resolve more than 1.6 million cells, enabling analysis lineages activation states distinct correlates, including survival. Using deep learning, can predict high accuracy those who will progress after surgery using a single 1-mm 2 core, which could be informative for management following surgical resection. Our dataset represents valuable resource non-small cell cancer research community exemplifies utility analyses. This study also highlights how artificial intelligence improve our understanding microenvironmental features that underlie progression may influence future practice.

Language: Английский

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Spatially resolved multi-omics highlights cell-specific metabolic remodeling and interactions in gastric cancer

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 10, 2023

Abstract Mapping tumor metabolic remodeling and their spatial crosstalk with surrounding non-tumor cells can fundamentally improve our understanding of biology, facilitates the designing advanced therapeutic strategies. Here, we present an integration mass spectrometry imaging-based metabolomics lipidomics microarray-based transcriptomics to hierarchically visualize intratumor heterogeneity cell interactions in same gastric cancer sample. Tumor-associated reprogramming is imaged at metabolic-transcriptional levels, maker metabolites, lipids, genes are connected pathways colocalized heterogeneous tissues. Integrated data from multi-omics approaches coherently identify types distributions within complex microenvironment, immune cell-dominated “tumor-normal interface” region where contact adjacent tissues characterized distinct transcriptional signatures significant immunometabolic alterations. Our approach for mapping tissue molecular architecture provides highly integrated picture heterogeneity, transform metabolism systemic level.

Language: Английский

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Mapping the genomic diaspora of gastric cancer

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 22(2), P. 71 - 84

Published: Oct. 26, 2021

Language: Английский

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Exhaustion-associated cholesterol deficiency dampens the cytotoxic arm of antitumor immunity

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(7), P. 1276 - 1293.e11

Published: May 26, 2023

Language: Английский

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scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 23, 2022

Abstract The tumor microenvironment (TME) in gastric cancer (GC) has been shown to be important for control but the specific characteristics GC are not fully appreciated. We generated an atlas of 166,533 cells from 10 patients with matched paratumor tissues and blood. Our results show tumor-associated stromal (TASCs) have upregulated activity Wnt signaling angiogenesis, negatively correlated survival. Tumor-associated macrophages LAMP3 + DCs involved mediating T cell form intercellular interaction hubs TASCs. Clonotype trajectory analysis demonstrates that Tc17 ( IL-17 CD8 cells) originate tissue-resident memory can subsequently differentiate into exhausted cells, suggesting alternative pathway exhaustion. indicate IL17 may promote progression through , IL22 IL26 signaling, highlighting possibility targeting associated pathways as a therapeutic strategy treat GC.

Language: Английский

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Advances in single-cell RNA sequencing and its applications in cancer research

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 24, 2023

Abstract Cancers are a group of heterogeneous diseases characterized by the acquisition functional capabilities during transition from normal to neoplastic state. Powerful experimental and computational tools can be applied elucidate mechanisms occurrence, progression, metastasis, drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect average gene expression in sample, making it difficult understand tumor heterogeneity microenvironment. The emergence development single-cell (scRNA-seq) technologies have provided opportunities subtle changes biology identifying distinct cell subpopulations, dissecting microenvironment, characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used cancer studies explore which increased understanding tumorigenesis evolution. This review summarizes basic processes their increasing applications research clinical practice.

Language: Английский

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Heterogeneity and plasticity of epithelial–mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(6)

Published: Feb. 19, 2023

Epithelial-mesenchymal transition (EMT) or mesenchymal-epithelial (MET) plays critical roles in cancer metastasis. Recent studies, especially those based on single-cell sequencing, have revealed that EMT is not a binary process, but heterogeneous and dynamic disposition with intermediary partial states. Multiple double-negative feedback loops involved by EMT-related transcription factors (EMT-TFs) been identified. These between drivers MET finely regulate the state of cell. In this review, general characteristics, biomarkers molecular mechanisms different states were summarized. We additionally discussed direct indirect tumour More importantly, article provides evidence heterogeneity closely related to poor prognosis gastric cancer. Notably, seesaw model was proposed explain how cells themselves remain specific states, including epithelial state, hybrid/intermediate mesenchymal state. Additionally, also review current status, limitations future perspectives signalling clinical applications.

Language: Английский

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