Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(4), P. 386 - 401

Published: April 28, 2022

Language: Английский

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Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(6), P. 866 - 882.e11

Published: April 29, 2021

Language: Английский

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A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma

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

Published: Aug. 6, 2022

Abstract Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and development. Here, we generate single-cell atlas multicellular ecosystem HCC from four tissue sites. We show enrichment central memory T cells (T CM ) in early tertiary lymphoid structures (E-TLSs) assess relationships chronic HBV/HCV infection cell infiltration exhaustion. find MMP9 + macrophages to be terminally differentiated tumor-associated (TAMs) PPARγ pivotal transcription factor driving their differentiation. also characterize heterogeneous subpopulations malignant hepatocytes multifaceted functions shaping immune HCC. Finally, identify seven microenvironment-based subtypes that can predict prognosis patients. Collectively, this large-scale deepens our understanding microenvironment, which might facilitate development new therapy strategies for malignancy.

Language: Английский

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Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(10), P. 5380 - 5396

Published: July 14, 2020

Immune checkpoint blockade (ICB) has revolutionized cancer therapeutics. Desmoplastic malignancies, such as cholangiocarcinoma (CCA), have an abundant tumor immune microenvironment (TIME). However, to date, ICB monotherapy in malignancies been ineffective. Herein, we identify tumor-associated macrophages (TAMs) the primary source of programmed death–ligand 1 (PD-L1) human and murine CCA. In a model CCA, recruited PD-L1+ TAMs facilitated CCA progression. TAM failed decrease progression due compensatory emergence granulocytic myeloid-derived suppressor cells (G-MDSCs) that mediated escape by impairing T cell response. Single-cell RNA sequencing (scRNA-Seq) G-MDSCs highlighted unique ApoE G-MDSC subset enriched with blockade; further analysis scRNA-Seq data set demonstrated presence similar Finally, dual inhibition potentiated ICB. summary, our findings highlight therapeutic potential coupling immunotherapies targeting immunosuppressive myeloid

Language: Английский

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Hepatocellular carcinoma: old friends and new tricks

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(12), P. 1898 - 1907

Published: Dec. 1, 2020

Abstract Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and a leading cause of cancer-related deaths worldwide. Ninety percent HCC cases arise from cirrhosis, during which cells undergo chronic cycles necrosis regeneration. The complex genomic landscape has been extensively investigated to draw correlations between recurrently mutated pathways patient prognosis. However, our limited success with targeted therapy shows that knowing presence somatic mutations alone insufficient for us gauge full spectrum their functional consequences in context tumor evolution. In addition, current molecular classification offers little information on relationship features immunological properties tumors immune microenvironment. This review introduces challenges advancements made surveillance, diagnosis, treatment. We also discuss suite HCC-associated genetic changes describe recent studies provide evidence an evolving model its implications understanding targeting progression.

Language: Английский

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Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 75(6), P. 1397 - 1408

Published: June 30, 2021

Language: Английский

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Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 17, 2021

Abstract Interaction between tumor cells and immune in the microenvironment is important cancer development. Immune interact with to shape this process. Here, we use single-cell RNA sequencing analysis delineate landscape heterogeneity a cohort of patients HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress T cell infiltration TIGIT-NECTIN2 interaction regulates immunosuppressive environment. The state transition towards more exhaustive status exemplifies overall cancer-promoting immunocellular landscape. Furthermore, global molecular profiles reveals co-existence intra-tumoral inter-tumoral heterogeneity, but apparent latter. This intercellular interactions provides mechanistic information for design efficacious immune-oncology treatments carcinoma.

Language: Английский

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Single-cell genomics and spatial transcriptomics: Discovery of novel cell states and cellular interactions in liver physiology and disease biology

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 73(5), P. 1219 - 1230

Published: June 10, 2020

Transcriptome analysis enables the study of gene expression in human tissues and is a valuable tool to characterise liver function dynamics during disease, as well identify prognostic markers or signatures, facilitate discovery new therapeutic targets. In contrast whole tissue RNA sequencing analysis, single-cell RNA-sequencing (scRNA-seq) spatial transcriptomics transcriptional activity at single cell level. ScRNA-seq has paved way for previously unknown types subtypes normal diseased liver, facilitating rare cells (such progenitor cells) functional roles non-parenchymal chronic disease cancer. By adding information scRNA-seq data, transformed our understanding organisation cell-to-cell interactions situ. These approaches have recently been applied investigate regeneration, hepatocytes cells, profile landscape diseases Herein, we review principles technologies behind transcriptomic approaches, highlighting recent discoveries novel insights these methodologies yielded both physiology biology.

Language: Английский

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Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 6, 2021

Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate composition ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs epithelial cells discover 42 cell types, including 26 immune 16 nonimmune stromal subtypes in microenvironment (TME), analyse interactions between cancer other among different types TME. Moreover, link to somatic mutations several markers significantly associated with patients' survival, which may be relevant precision care patients. These results reveal immunosuppressive status TME further our understanding ESCC.

Language: Английский

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Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 17(8), P. 457 - 472

Published: June 1, 2020

Language: Английский

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