Abstract:
BACKGROUND:Kaposi's Sarcoma Herpesvirus (KSHV) is a gammaherpesvirus strongly linked to human cancer. The virus is also able to induce immune suppression, effect that contributes to onset/progression of the viral-associated malignancies. As KSHV may infect macrophages and these cells abundantly infiltrate Kaposi's sarcoma lesions, in this study we investigated whether KSHV-infection could affect macrophage polarisation to promote tumorigenesis. METHODS:FACS analysis was used to detect macrophage markers and PD-L1 expression. KSHV infection and the molecular pathways activated were investigated by western blot analysis and by qRT-PCR while cytokine release was assessed by Multi-analyte Kit. RESULTS:We found that KSHV infection reduced macrophage survival and skewed their polarisation towards M2 like/TAM cells, based on the expression of CD163, on the activation of STAT3 and STAT6 pathways and the release of pro-tumorigenic cytokines such as IL-10, VEGF, IL-6 and IL-8. We also found that KSHV triggered Ire1 α-XBP1 axis activation in infected macrophages to increase the release of pro-tumorigenic cytokines and to up-regulate PD-L1 surface expression. CONCLUSIONS:The findings that KSHV infection of macrophages skews their polarisation towards M2/TAM and that activate Ire1 α-XBP1 to increase the release of pro-tumorigenic cytokines and the expression of PD-L1, suggest that manipulation of UPR could be exploited to prevent or improve the treatment of KSHV-associated malignancies.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Gilardini Montani MS,Falcinelli L,Santarelli R,Granato M,Romeo MA,Cecere N,Gonnella R,D'Orazi G,Faggioni A,Cirone Mdoi
10.1038/s41416-020-0872-0subject
Has Abstractpub_date
2020-07-01 00:00:00pages
298-306issue
2eissn
0007-0920issn
1532-1827pii
10.1038/s41416-020-0872-0journal_volume
123pub_type
杂志文章abstract:BACKGROUND:defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene MUTYH are responsible for MUTYH-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested MUTYH mono-allelic variants to be low penetrance ...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/sj.bjc.6605966
更新日期:2010-12-07 00:00:00
abstract::Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and ability to inhibit a tumour...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602383
更新日期:2005-02-28 00:00:00
abstract::In small-cell lung cancer cell lines resistance to growth inhibition by transforming growth factor (TGF)-beta 1, was previously shown to correlate with lack of TGF-beta receptor I (RI) and II (RII) proteins. To further investigate the role of these receptors, the expression of mRNA for RI, RII and beta-glycan (RIII) w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.201
更新日期:1996-05-01 00:00:00
abstract::The appearance of a liver DNA synthesis promoter (HP) in rat plasma after dimethylnitrosamine (DMNA) or thioacetamide injection was investigated. After 48 h, DMNA (30 mg kg-1 body weight) produced liver (centrilobular) necrosis and intense hepatic regeneration, as assessed by microscopic observations of liver slices, ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.122
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND:Risk factors for the development of myelodysplastic syndromes (MDS) include age, exposure to ionising radiation, and cytotoxic drug treatment. Recently, asthma also has been suggested as a risk factor for MDS. METHODS:We undertook this nationwide population-based cohort study on patients with a first-time h...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.389
更新日期:2017-01-03 00:00:00
abstract::Basal cell carcinomas (BCCs) are very frequent cutaneous cancers, often located on the face. Cure rates with surgery and radiotherapy are high, but these treatments have never been compared prospectively. A randomized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of th...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/bjc.1997.343
更新日期:1997-01-01 00:00:00
abstract::The important role of the p53 gene in tumour progression and cellular response to DNA damage has prompted investigation of the clinical significance of alterations to this gene. We examined both p53 overexpression and mutation of the gene in endometrial carcinoma in order to evaluate the prognostic significance of the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.401
更新日期:1996-08-01 00:00:00
abstract::The phenotypic expression of cells derived from human anaplastic astrocytomas, rat glioma, normal human adult and foetal brain tissue have been examined for differentiated and malignancy-associated properties. Glial fibrillary acidic protein (GFAP), high affinity glutamate and gamma-amino butyric acid (GABA) uptake an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.44
更新日期:1984-03-01 00:00:00
abstract:BACKGROUND:Mesothelin is expressed in various types of malignant tumour, and we recently reported that expression of mesothelin was related to an unfavourable patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined the clinicopathological significance of the mesothelin expression in gastric canc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.235
更新日期:2012-06-26 00:00:00
abstract:BACKGROUND:Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported. METHODS:We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.27
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.144
更新日期:2013-05-28 00:00:00
abstract::The tumour-suppressor gene TP53 is frequently mutated in breast tumours, and the majority of the mutations are clustered within the core domain, the region involved in DNA binding. We searched for alterations in this central domain of the TP53gene in 222 human breast cancer specimens using polymerase chain reaction-si...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.187
更新日期:1998-04-01 00:00:00
abstract::Clinico-cytogenetic correlations were assessed in 88 patients with malignant ovarian tumours. Cytogenetic analysis of the primary tumours yielded normal karyotype (N) in 33 patients and abnormal karyotypes (A) in 55 patients. Within the A group, seven tumours had simple abnormalities (AS), i.e., numerical changes only...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.56
更新日期:1992-02-01 00:00:00
abstract:BACKGROUND:Early detection of non-small-cell lung cancer (NSCLC) and accurate prognostic risk assessment could improve patient outcome. We examined the significance of urinary N(1), N(12)-diacetylspermine (DiAcSpm) in the detection and prognostic stratification of NSCLC patients. METHODS:A DiAcSpm/cutoff ratio (DASr) ...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2015.349
更新日期:2015-11-17 00:00:00
abstract:BACKGROUND:Radio- and chemotherapy (RT/CT) resistance hampers success in combating small and non-small cell lung cancers (SCLC/NSCLC). The underlying molecular mechanisms of RT/CT resistance of LCs are multifactorial and have been understood in part hitherto. miRNAs, key regulators of mRNAs, are well-recognised oncomir...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.382
更新日期:2012-10-09 00:00:00
abstract::The serum CA125 level was determined by a one-step immunoradiometric assay method in patients with lung cancer. Increased serum CA125 levels were observed in 37.8% of patients with squamous cell cancer, in 30.0% of those with adenocarcinoma and in 60.0% of those with small call cancer. Most patients with increased ser...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.355
更新日期:1990-10-01 00:00:00
abstract:BACKGROUND:Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in breast cancer. However, the function of PRRX1 in colorectal cancer (CRC) has not been elucidated. METHODS:We utilised ectopic PRRX1-expressing cell lines to analyse the function of PRRX1 in CRC...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.339
更新日期:2013-07-23 00:00:00
abstract::The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690008
更新日期:1999-01-01 00:00:00
abstract::We evaluated the risk of bladder cancer in a cohort of 79,280 Swedish men hospitalised for benign prostatic hyperplasia (BPH), identified in the Swedish Inpatient Register between 1964 and 1983 and followed until 1989 via multiple record linkages with nationwide data on cancer registry, death and emigration. Standardi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603730
更新日期:2007-05-07 00:00:00
abstract::Gallium-67 is a radionuclide that accumulates in haematological malignancies and is used for diagnostic purposes. Uptake of 67Ga into the cell occurs via the transferrin receptor, which is differentially expressed during the various cell cycle phases. With the aim of selectively increasing 67Ga uptake, we studied whet...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.411
更新日期:1996-08-01 00:00:00
abstract::Studies of underground miners occupationally exposed to radon have consistently demonstrated an increased risk of lung cancer in both smokers and non-smokers. Radon exposure also occurs elsewhere, especially in houses, and estimates based on the findings for miners suggest that residential radon is responsible for abo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.506
更新日期:1998-08-01 00:00:00
abstract::The prognostic value of several clinical and histopathological characteristics has been evaluated in patients with Dukes' B and C carcinoma of the rectum and the rectosigmoid. Data on 260 Dukes' B and 208 Dukes' C tumours entered into a prospective, randomized clinical trial of post-operative radiotherapy (50 Gy given...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.192
更新日期:1988-08-01 00:00:00
abstract::The establishment and characterisation (morphology, ultrastructure, tumourigenicity) of six cell lines from primary human colorectal adenocarcinomas is described. These lines were established from surgical specimens, from 49 unselected patients, without the use of 'feeder' cells, 'conditioned' medium or passage of cel...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.132
更新日期:1986-06-01 00:00:00
abstract:BACKGROUND:Laminin-5 (Ln5), a heterotrimer composed of three chains (α3, β3, and γ2), is a major component of the basement membrane in most adult tissues. One of the chains, Ln5-γ2, is a marker of invasive tumours because it is frequently expressed as a monomer in malignant tumours. Recent studies from our laboratories...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.283
更新日期:2011-09-06 00:00:00
abstract::HER2/neu-derived peptides inducing MHC class II-restricted CD4+ T helper lymphocyte (Th) responses, although critical for tumour rejection, are not thoroughly characterized. Here, we report the generation and characterization of CD4+ T cell clones specifically recognizing a HER-2/neu-derived peptide (776-788) [designa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2089
更新日期:2001-11-16 00:00:00
abstract::Caveolin-1 and -2 (CAV1, CAV2) are closely linked genes localised to the fragile region of 7q31 (FRA7G), and loss of heterozygosity involving this region has been reported in breast cancer. Several studies have suggested that CAV1 is a negative regulator of HER2/neu signal transduction in vitro. However, the clinical ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602029
更新日期:2004-08-31 00:00:00
abstract:BACKGROUND:Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAFV600-mutant advanced melanoma. Until now, data are inconclusive on which therapy to use as first-line treatment. The aim of this study was to use propensity score matching to compare first-line an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-01229-1
更新日期:2021-01-26 00:00:00
abstract:BACKGROUND:Accurate assessment of the prevalence of the human papilloma virus (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC are consistently associated with an improved overall survival. Recently, an algorithm has become available that reliably detects clinically relevant HPV in tumour ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.99
更新日期:2015-04-14 00:00:00
abstract::EWS-Fli-1, a fusion gene found in Ewing's sarcoma and primitive neuro-ectodermal tumour (PNET), encodes a transcriptional activator and promotes cellular transformation. We have made stable Ewing's sarcoma cells expressing antisense EWS-Fli-1 transcripts by transfecting the antisense EWS-Fli-1 expression plasmid. Thes...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.1998.0870
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Patients with malignant pleural effusions (MPEs) generally have advanced disease with poor survival and few therapeutic options. Cells within MPEs may be used to stratify patients for targeted therapy. Targeted therapy with poly(ADP ribose) polymerase inhibitors (PARPi) depends on identifying homologous reco...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.261
更新日期:2014-07-08 00:00:00