Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Single-Cell Atlas of the Multicellular Ecosystem of Primary and Metastatic Hepatocellular Carcinoma

ABSTRACT: Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment and tumor development. Here, we generated > 70,000 single-cell transcriptomes for 10 HCC patients from four relevant sites: primary tumor, portal vein tumor thrombus (PVTT), metastatic lymph node and non-tumor liver. We discovered a cluster of antitumor central memory T cells enriched in intratumoral tertiary lymphoid structures (TLSs) of HCC. We found chronic HBV/HCV infection increases the infiltration of CD8+ T cells in tumors but aggravates the exhaustion of tumor-infiltrating lymphocytes. We identified MMP9+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and two distinct differentiation trajectories are related to their accumulation. We further demonstrated MMP9+ TAMs can promote HCC cells migration, invasion and angiogenesis. Our data also revealed the heterogeneous population of malignant hepatocytes and found they might play multifaceted roles in shaping the immune microenvironment of HCC. Finally, we identified seven TME subtypes of HCC that can predict patient prognosis. Collectively, this large-scale, single-cell atlas deepens our understanding of the ecosystem in primary and metastatic HCCs, might facilitating identification of new immune therapy strategies for this malignancy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149614 | GEO | 2020/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A Single-Cell Atlas of the Multicellular Ecosystem of Primary and Metastatic Hepatocellular Carcinoma

Project description:Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generated a single-cell atlas of the multicellular ecosystem of HCCs from four relevant sites. Antitumor central memory T (TCM) cells were found in tertiary lymphoid structures (TLSs). Chronic HBV/HCV infection increases infiltration of CD8+ T cells in tumors but aggravates T cell exhaustion. We identified CD11b+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and two distinct differentiation trajectories contribute to their accumulation. We further demonstrated CD11b+ TAMs promote HCC cells invasion and migration, and angiogenesis. We characterized the heterogeneous subpopulations of malignant hepatocytes and their multifaceted roles in shaping the immune microenvironment. Finally, we identified seven TME subtypes that can predict patient prognosis. Collectively, this large-scale atlas deepens our understanding of the ecosystem in primary and metastatic HCCs, might facilitating the development of new immune therapy strategies for this malignancy.

| EGAS00001004468 | EGA

S100A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma

Project description:Tumor-associated macrophages (TAMs) are crucial components of the tumor microenvironment (TME). They play vital roles in hepatocellular carcinoma (HCC) progression. However, the interactions between TAMs and HCC cells have not been fully characterized. In this study, TAMs were induced using human monocytic cell line THP-1 cells in vitro to investigate their functions in HCC progression. S100 calcium binding protein A9 (S100A9), an inflammatory microenvironment-related secreted protein, was identified to be significantly upregulated in TAMs. S100A9 expression in tumor tissues was associated with poor survival of HCC patients. It could enhance the stem cell-like properties of HepG2 and MHCC-97H cells by activating nuclear factor-kappa B (NF-κB) signaling pathway through advanced glycosylation end-product specific receptor (AGER) in a Ca2+-dependent manner. Furthermore, we found that, after treatment with S100A9, HepG2 and MHCC-97H cells recruited more macrophages via chemokine (C-C Motif) ligand 2 (CCL2), which suggests a positive feedback between TAMs and HCC cells. Taken together, our findings reveal that TAMs could upregulate secreted protein S100A9 and enhance the stem cell-like properties of HCC cells, and provide a potential therapeutic target for combating HCC.

2020-10-23 | GSE158792 | GEO

S100A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma (RNA-Seq)

Project description:Tumor-associated macrophages (TAMs) are crucial components of the tumor microenvironment (TME). They play vital roles in hepatocellular carcinoma (HCC) progression. However, the interactions between TAMs and HCC cells have not been fully characterized. In this study, TAMs were induced using human monocytic cell line THP-1 cells in vitro to investigate their functions in HCC progression. S100 calcium binding protein A9 (S100A9), an inflammatory microenvironment-related secreted protein, was identified to be significantly upregulated in TAMs. S100A9 expression in tumor tissues was associated with poor survival of HCC patients. It could enhance the stem cell-like properties of HepG2 and MHCC-97H cells by activating nuclear factor-kappa B (NF-κB) signaling pathway through advanced glycosylation end-product specific receptor (AGER) in a Ca2+-dependent manner. Furthermore, we found that, after treatment with S100A9, HepG2 and MHCC-97H cells recruited more macrophages infiltration via chemokine (C-C Motif) ligand 2 (CCL2), which suggests a positive feedback between TAMs and HCC cells. Taken together, our findings reveal that TAMs could upregulate S100A9 and enhance the stem cell-like properties of HCC cells, and provide a potential therapeutic target for combating HCC.

2020-10-23 | GSE159264 | GEO

Expression analysis of tumor-associated macrophages from primary tumor and metastatic lung

Project description:In tumor microenvironment, tumor-associated macrophages (TAMs) have been characterized as M1-like or M2-like phenotype. In this study, we investigated the characteristics and functional roles of different TAMs on cancer metastasis. We isolated TAMs from primary tumor and metastatic lung and performed microarrays to identify the gene expression in distinct TAMs populations.

2018-07-26 | GSE96944 | GEO

Comparison of Invasive TAM sub-population to General TAM population

Project description:The tumor microenvironment modifies the malignancy of tumors. In solid tumors this environment is populated by many macrophages (tumor-associated macrophages; TAMs) that in genetic studies that depleted these cells from mouse models of breast cancer were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these effects are through the stimulation of tumor cell migration, invasion, intravasation as well as an enhancement of angiogenesis. Using an in vivo invasion assay it was demonstrated that invasive carcinoma cells are a unique sub-population of tumor cells whose invasion and chemotaxis is dependent upon the co-migration of TAMs with obligate reciprocal signaling through an EGF/CSF-1 paracrine loop. In this study these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison to TAMs isolated indiscriminately to function using established macrophage markers by flow cytometry. Five biological replicates for each population (Invasive and General TAM) were used.

2010-05-16 | E-GEOD-18295 | biostudies-arrayexpress

The gene expression of HCC cells and HCC cells knocked down TMED3

Project description:We report that TMED3 was up-regulated in HCC and portal vein tumor thrombus. Gene microarray analysis TMED3-knockdown cells and normal HCC cell.

2017-02-09 | GSE88772 | GEO

Blocking CX3CR1+ Tumor-associated Macrophages Synergize with anti-PD-1 Therapy in Hepatocellular Carcinoma

Project description:The efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) treatment remains limited, warranting further investigation into the underlying mechanisms. Accumulating evidence indicates that myeloid cells within the tumor microenvironment (TME) play a role in immune evasion and treatment resistance. In this study, we aimed to explore the contribution of tumor-associated macrophages (TAMs) in the HCC TME. Our findings unveil the critical involvement of CX3C motif chemokine receptor 1 (CX3CR1)-positive TAMs in inducing T cell exhaustion through interleukin-27 (IL-27) secretion, providing valuable insights into the mechanisms underlying the suboptimal efficacy of anti-PD-1 therapy in HCC. Additionally, we identified prostaglandin E2 (PGE2) released by immune-attacked tumor cells as a key driver of CX3CR1+ TAM recruitment. To enhance the therapeutic response to current anti-PD-1 therapy, we propose a novel treatment strategy that combines targeted depletion of CX3CR1+ TAMs with anti-PD-1 therapy. Overall, our study contributes to the understanding of TAMs' role in cancer immunotherapy and presents potential clinical implications for HCC treatment. By targeting CX3CR1+ TAMs in conjunction with anti-PD-1 therapy, we have the potential to enhance the effectiveness of immunotherapeutic interventions in HCC patients.

2024-07-25 | GSE263240 | GEO

Gene expression profiling of CD8+ T cells in the Norathyriol versus PBS-treated co-culture system

Project description:Metabolic reprogramming fuels cancer cell metastasis and remodels the immunosuppressive tumor microenvironment (TME). We report here that a circRNA, circPETH, packaged by extracellular vesicles (EVs) from tumor-associated macrophages (TAMs) to hepatocellular carcinoma (HCC) cells, facilitates glycolysis and metastasis of recipient HCC cells. Mechanistically, circPETH-147aa, encoded by circPETH in a m6A-driven manner, promotes PKM2-catalyzed ALDOA-S36 phosphorylation via MEG pocket. Furthermore, circPETH-147aa impairs anti-HCC immunity by elevating HuR-dependent SLC43A2 mRNA stability and driving methionine and leucine deficiency in cytotoxic CD8+ T cells. Importantly, by virtual and experimental screening, we found that the novel small-molecule Norathyriol was an effective inhibitor that targets the MEG pocket on circPETH-147aa surface. Norathyriol reverses circPETH-147aa-facilitated acquisition of metabolic and metastatic phenotypes for HCC cells, increases anti-PD1 efficacy and boosts cytotoxic CD8+ T-cell function. Our findings determine Norathyriol as a promising anti-HCC agent that contributes to the attenuation of advanced HCC resistance to immune checkpoint blocker (ICB) therapies.

2024-09-01 | GSE242130 | GEO

Gene expression profiling for circPETH overexpression and knockout

Project description:Metabolic reprogramming fuels cancer cell metastasis and remodels immunosuppressive tumor microenvironment (TME). We report here that a circRNA packaged by extracellular vesicles (EVs) from tumor-associated macrophages (TAMs) to hepatocellular carcinoma (HCC) cells, circPETH, facilitates glycolysis and metastasis of HCC cells. Mechanistically, circPETH-147aa, encoded by circPETH in m6A-driven manner, promotes the PKM2-catalyzed ALDOA-S36 phosphorylation via MEG pocket. Furthermore, circPETH-147aa impairs anti-HCC immunity by elevating the HuR-dependent SLC43A2-mRNA stability and stimulating the deficiency of methionine and leucine in cytotoxic CD8+ T cells. Importantly, we successfully identified a novel small molecule, Norathyriol, by virtual and experimental screening as an effective inhibitor targeting MEG pocket on circPETH-147aa surface. Norathyriol reverses circPETH-147aa-facilitated metabolic and metastatic phenotypes of HCC cells, improves anti-PD1 efficacy and boosts cytotoxic CD8+ T cells function. Our findings determine Norathyriol as a promising anti-HCC agent, and contribute to overcoming the resistance of advanced HCC to immune checkpoint blockades (ICBs) therapies.

2024-08-29 | GSE242016 | GEO

Gene expression profile of RAW264.7 monocytes treated with or without IL-33

Project description:Molecular mechanisms underlying the cancer stroma in metastasis is largely unknown. Here we show that cancer-associated fibroblasts (CAFs) produce high levels of IL-33 that acted on tumor-associated macrophages (TAMs) to induce the M1 to M2 transition. Genome profiling of metastasis-related genes in the IL-33-stimulated TAMs showed a > 200-fold increase of metalloproteinase 9 (MMP9). Signaling analysis demonstrated the IL-33-ST2-NFkB-MMP9-laminin pathway that mediates cancer metastasis. In mouse and human fibroblast-rich pancreatic cancers, genetic deletion of IL-33, ST2 and MMP9 markedly blocked metastasis. Pharmacological inhibition of NFkB and MMP9 also blocked cancer metastasis. Deletion of IL-33, ST2 and MMP9 restored laminin, a key basement membrane component associated to tumor microvessels. Together, our data provide novel mechanistic insights on the IL-33-NFkB-MMP9-laminin axis that mediates the CAF-TAM-committed cancer metastasis. Thus, targeting the CAF-TAM-vessel interaction provides an outstanding therapeutic opportunity for cancer treatment.

2018-11-30 | GSE97657 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data