Abstract:
BACKGROUND & AIMS:Macrophages (Mϕ) represent a major component of tumor tissues and play an important role in both tumor progression and therapeutic response. Although tumor Mϕ are generally considered to be derived from circulating monocytes, emerging evidence indicates that tissue Mϕ pools can be maintained by self-renewal. We aimed to elucidate the contribution, phenotype, and regulatory mechanisms of proliferating Mϕ in human hepatocellular carcinoma (HCC). METHODS:Flow cytometry analyses were performed to examine the presence and phenotype of proliferating Mϕ in fresh HCC tissues. Dual immunofluorescence staining was applied to analyze the prognostic value of proliferating Mϕ. The underlying regulatory mechanisms were examined using human monocyte-derived Mϕ. RESULTS:Tumor-infiltrating Mϕ exhibited a significantly higher proliferative capacity than Mϕ in non-tumor tissues. A higher level of Mϕ proliferation was positively correlated with Mϕ density in the tumor and a poor prognosis in patients with HCC. Proliferating Mϕ were less differentiated (with increased CD206 expression) and were induced by the tumor cell-derived soluble small molecule, adenosine, but not proteins, lipids, or large peptides. Mechanistic studies demonstrated that autocrine granulocyte-macrophage colony-stimulating factor (GM-CSF) released by tumor-stimulated Mϕ could enhance A2A receptor expression on Mϕ and function synergistically with adenosine to elicit Mϕ proliferation in HCC. CONCLUSIONS:Local Mϕ proliferation is an important mechanism for Mϕ accumulation in HCC tissues. Tumor-derived adenosine functions synergistically with autocrine GM-CSF released from activated Mϕ, which promotes Mϕ proliferation. Thus, selective modulation of Mϕ accumulation at the source may provide a novel strategy for cancer therapy. LAY SUMMARY:Tumor-associated macrophages (TAMs) have been reported to play an essential role in both tumor progression and therapeutic response. A fundamental understanding of the mechanisms that regulate macrophage accumulation in tumors will undoubtedly lead to the development of strategies to target macrophages with high specificity and efficiency. The current study unveils a novel mechanism by which local proliferation is linked to macrophage accumulation in the tumor milieu, identifying potential targets for future immune-based anticancer therapies.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Wang J,Wang Y,Chu Y,Li Z,Yu X,Huang Z,Xu J,Zheng Ldoi
10.1016/j.jhep.2020.10.021subject
Has Abstractpub_date
2020-10-31 00:00:00eissn
0168-8278issn
1600-0641pii
S0168-8278(20)33739-9pub_type
杂志文章abstract:BACKGROUND & AIMS:Little is known about the frequency, phenotype and function of HBV-specific B cells during chronic infection. Here we study HBcAg and HBsAg-specific B cells in different clinical phases of a chronic HBV infection. METHODS:We included 118 treatment naïve and 34 nucleos(t)ide analogue-treated patients ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.01.024
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND & AIMS:Weak hepatitis C virus (HCV) specific immunity in peripheral blood has been shown to be partially controlled by regulatory T cells (Treg). However, little is known about Treg present in livers of HCV-infected patients, their association with clinical parameters, and immunopathology resulting in diseas...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.12.013
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND/AIMS:In hepatitis C infection, the production of inappropriate cytokine levels appears to contribute to viral persistence and to affect the response to antiviral therapy. Additionally, polymorphisms in the cytokine genes may affect the production of the cytokines. In this study, we determined the frequency o...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00243-4
更新日期:2002-02-01 00:00:00
abstract::The reversibility and time course of the adaptive changes in hepatic bile salt transport related to modifications of the bile salt enterohepatic circulation and bile salt pool size have not been previously studied. For this reason a model of reversible interruption of entero-hepatic circulation was characterized in un...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80182-5
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND & AIMS:Liver macrophages can be involved in both pathogen clearance and/or pathogenesis. To get further insight on their role during chronic hepatitis B virus (HBV) infections, our aim was to phenotypically and functionally characterize in vivo and ex vivo the interplay between HBV, primary human liver macro...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.06.032
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND/AIMS:Vaccination strategies able to induce strong T-cell responses might contribute to eradicate hepatitis C virus (HCV) infection. We previously demonstrated that fusion of an antigen to the extra domain A from fibronectin (EDA) targets the antigen to TLR4-expressing dendritic cells (DC) and improves its im...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.06.005
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND & AIMS:Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the lig...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.02.012
更新日期:2014-06-01 00:00:00
abstract::Liver fibrosis is one of the most important factors of disturbed liver function, but could not be measured by simple blood tests until recently. Among several parameters used for this purpose, the aminoterminal procollagen type III peptide (PIIIP) appears to be the most widely accepted. Studies conducted in several cl...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(85)80069-6
更新日期:1985-01-01 00:00:00
abstract::There are three main types of interferon, now designated alpha, beta and gamma. Human interferons-alpha exist as many subtypes, probably more than 26. These are chemically quite closely related, but each has a unique chemical composition and biological properties. Preparations of interferon-alpha derived from stimulat...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(86)80115-5
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND/AIMS:Because dietary modifications have prolonged the life expectancy of patients with glycogen storage disease type Ia (GSD Ia), the incidence of hepatocellular adenoma (HCA) to carcinoma (HCC) transformation is increasing. The objective of this retrospective study is to assess the safety and effectiveness ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.05.012
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND/AIMS:Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. Interferon-alfa therapy may prevent the progression of the disease. The expressions of decorin and alfa-smooth muscle cell actin of the extracellular matrix play a central role in liver fibrosis. We set out to assess the expressions...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80104-x
更新日期:2000-06-01 00:00:00
abstract::In a follow-up study of 3 years' duration, serum inhibitory factors (SIF) were analysed in 23 patients with a protracted course of viral hepatitis B (PVH) and 12 patients with chronic persistent hepatitis (CPH). Four patients showed a progressive course, developing chronic active hepatitis, and one died of liver failu...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80083-1
更新日期:1987-04-01 00:00:00
abstract:BACKGROUND/AIMS:We previously showed that in cultured human myofibroblasts (hMFBs), Oncostatin M (OSM)-stimulated collagen accumulation is associated with increased tissue inhibitor of metalloproteinase (TIMP)1 message. However, the mechanism is unknown. METHODS:hMFBs were isolated by outgrowth from cirrhotic liver ex...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00265-3
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND & AIMS:Acetaminophen (APAP)-induced liver injury is the most frequent cause of acute liver failure in the US and many other countries. Metabolism of APAP results in formation of APAP protein adducts (APAP-AD) in hepatocytes and triggers mitochondrial dysfunction and necrosis. However, the mechanisms for how ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.04.025
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND/AIMS:Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains unknown. Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis. METHODS:Filipin ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.12.016
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.02.021
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND & AIMS:Aberrant activation of the RAS pathway is ubiquitous in human hepatocarcinogenesis, but the molecular mechanisms leading to RAS induction in the absence of RAS mutations remain under-investigated. We defined the role of Ras GTPase activating proteins (GAPs) in the constitutive activity of Ras signalin...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.06.036
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND & AIMS:Data on the natural history of chronic hepatitis C virus (HCV) genotype 6 is lacking. METHODS:We compared the natural history of 138 HCV genotype 1 patients (median age: 50) with 78 HCV genotype 6 patients (median age: 46.5). Baseline demographic data including gender, route of transmission, liver bi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.009
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.11.024
更新日期:2020-11-25 00:00:00
abstract::Two patients presented with neonatal cholestasis and acholic stools as first manifestations of McCune-Albright syndrome. Both went through an extensive evaluation including an exploratory laparotomy with peroperative cholangiography which ruled out biliary atresia. One patient presented from the fourth month of life w...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80202-0
更新日期:2000-01-01 00:00:00
abstract::The present study was conducted to evaluate if the increased rate of apoptosis previously reported in the liver of ethanol-treated rats was accompanied by increased cell renewal. A quantitative analysis of apoptosis was performed in rats fed an ethanol-containing liquid diet for 5 weeks. S-phase cells were demonstrate...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80498-2
更新日期:1994-04-01 00:00:00
abstract:BACKGROUND & AIMS:Recent research has suggested that dietary fructose intake may increase serum uric acid (UA) concentrations. Both UA concentration and fructose consumption maybe also increase in NAFLD. It is not known whether dietary fructose consumption and UA concentration are independently associated with non-alco...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.12.025
更新日期:2017-05-01 00:00:00
abstract::A diagnostic test has been developed to detect hepatitis B virus (HBV) DNA in human sera. This test involves a dot-blot technique in which non-radioactive nucleic acid labelled with 2-acetylaminofluorene (AAF) is used as probe. Two series of human sera from 228 blood donors and 113 HBsAg chronic carriers were tested b...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80573-1
更新日期:1987-10-01 00:00:00
abstract::Interleukin 6 (IL-6) is a pleiotropic four-helix-bundle cytokine that exerts multiple functions in the body. In the liver, IL-6 is an important inducer of the acute phase response and infection defense. IL-6 is furthermore crucial for hepatocyte homeostasis and is a potent hepatocyte mitogen. It is not only implicated...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2016.02.004
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND & AIMS:It is established that cirrhotic patients who respond to beta-blockers by lowering their hepatic venous pressure gradient (HVPG) to < or =12 mmHg or by > or =20% of the baseline values are protected from bleeding. However, it is not known whether the effect remains unchanged over the treatment period....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.10.014
更新日期:2010-01-01 00:00:00
abstract::Liver disease is common in patients with cystic fibrosis, but the pathogenesis is poorly understood. The chronic colonization of bacteria in the lower airways leads to repeated treatments with antibiotics, especially aminoglycosides in high dosages. To investigate the possible role of aminoglycoside treatment in the n...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80058-3
更新日期:1994-02-01 00:00:00
abstract:BACKGROUND/AIMS:Chronic hepatitis C virus infections are often associated with extra-hepatic immunological manifestations, including various autoimmune disorders. The aims of this study were: (i) to determine the prevalence of hepatitis C virus markers in patients with autoimmune thrombocytopenic purpura, and (ii) to d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80027-1
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND/AIMS:Liver negative-strand hepatitis C virus (HCV) RNA is the most direct indicator of active viral replication but has only been examined in a few semiquantitative studies. METHODS:Positive- and negative-strand HCV RNA in the right (R) and left (L) liver lobes was quantified by rTth-based strand-specific r...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.10.014
更新日期:2006-02-01 00:00:00
abstract::Drug hepatotoxicity is partially determined by genetic factors involved in drug metabolism, which may involve the debrisoquine oxidation polymorphism mediated by cytochrome (CYP) 2D6. The purpose of this study was to assess the relationship between drug hepatotoxicity and another genetic polymorphism of drug oxidation...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80620-8
更新日期:1994-12-01 00:00:00
abstract::Chronic cholestatic diseases, whether occurring in infancy, childhood or adulthood, are characterized by defective bile acid transport from the liver to the intestine, which is caused by primary damage to the biliary epithelium in most cases. In this article, approaches to diagnosis and management of the main specific...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(00)80421-3
更新日期:2000-01-01 00:00:00