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1.
Jiabo Di Tjitske Duiveman-de Boer Carl G Figdor Ruurd Torensma 《World journal of stem cells》2013,5(4):149-162
Ovarian cancer accounts for only 3% of all cancers in women, but it causes more deaths than any other gynecologic cancer. Treatment with chemotherapy and cytoreductive surgery shows a good response to the therapy. However, in a large proportion of the patients the tumor grows back within a few years. Cancer stem cells, that are less responsive to these treatments, are blamed for this recurrence of disease. Immune therapy either cellular or humoral is a novel concept to treat cancer. It is based on the notice that immune cells invade the tumor. However, the tumor invest heavily to escape from immune elimination by recruiting several immune suppressive mechanisms. These processes are normally in place to limit excessive immune activation and prevent autoimmune phenomena. Here, we discuss current knowledge about the immune (suppressive) status in ovarian cancer. Moreover, we discuss the immunological targets of ovarian cancer stem cells. 相似文献
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Purpose To test the hypothesis that decrease in DNA methylation will increase the expression of cancer-testis antigens (CTA) and class
I major histocompatibility complex (MHC)-encoded molecules by ovarian cancer cells, and thus increase the ability of these
cells to be recognized by antigen-reactive CD8+ T cells.
Methods Human ovarian cancer cell lines were cultured in the presence or absence of varying concentrations of the DNA demethylating
agent 5-aza-2′-deoxycytidine (DAC) for 3–7 days. The expression levels of 12 CTA genes were measured using the polymerase
chain reaction. The protein expression levels of class I MHC molecules and MAGE-A1 were measured by flow cytometry. T cell
reactivity was determined using interferon-γ ELISpot analysis.
Results DAC treatment of ovarian cancer cell lines increased the expression of 11 of 12 CTA genes tested including MAGE-A1, MAGE-A3,
MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, NY-ESO-1, TAG-1, TAG-2a, TAG-2b, and TAG-2c. In contrast, DAC treatment decreased the
already low expression of the MAGE-A2 gene by ovarian cancer cells, a finding not previously observed in cancers of any histological
type. DAC treatment increases the expression of class I MHC molecules by the cells. These effects were time-dependent over
a 7-day interval, and were dose-dependent up to 1–3 μM for CTA and up to 10 μM for class I MHC molecules. Each cell line tested
had a unique pattern of gene upregulation after exposure to DAC. The enhanced expression levels increased the recognition
of 2 of 3 antigens recognized by antigen-reactive CD8+ T cells.
Conclusions These results demonstrate the potential utility of combining DAC therapy with vaccine therapy in an attempt to induce the
expression of antigens targeted by the vaccine, but they also demonstrate that care must be taken to target inducible antigens.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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Interleukin-10 in serous ovarian carcinoma cell lines 总被引:7,自引:1,他引:6
Berger S Siegert A Denkert C Köbel M Hauptmann S 《Cancer immunology, immunotherapy : CII》2001,50(6):328-333
Interleukin-10, one of the most potent anti-inflammatory cytokines, is expressed in ovarian carcinomas in vivo. In contrast to the high levels of IL-10 in ascites and tumour tissue, the expression of this cytokine appears to be a rare
event in ovarian carcinoma cell lines in vitro. Virtually nothing is known about the regulation of IL-10 expression in ovarian
carcinoma cell lines. We investigated the expression of IL-10 in four cell lines originally derived from ovarian serous adenocarcinoma:
OVCAR-3, SKOV-3, CAOV-3 and OAW-42. IL-10-specific mRNA was detected in OVCAR-3 and only this cell line produced IL-10 constitutively
under serum-free conditions as well as in serum-containing medium. Our studies on the regulation of IL-10 secretion in OVCAR-3
revealed that (1) proinflammatory stimuli IL-1β and TNF-α, but not LPS, enhance IL-10 secretion, (2) IL-6 has no influence on the release of IL-10, (3) prostaglandin E2 influences
neither the spontaneous nor the TNF-α- or IL-1β-stimulated IL-10 production and (4) interferon-γ inhibits IL-10 secretion. We conclude that only a minority of serous ovarian carcinoma cells maintain the ability to produce
IL-10 in vitro. Our data on the regulation of IL-10 production in OVCAR-3 indicate that ovarian carcinoma cells share some, but not all,
of the regulatory features typical for the monocytic IL-10 secretion.
Received: 1 February 2001 / Accepted: 29 March 2001 相似文献
5.
Algarra I García-Lora A Cabrera T Ruiz-Cabello F Garrido F 《Cancer immunology, immunotherapy : CII》2004,53(10):904-910
Tumor immune escape variants can be identified in human and experimental tumors. A variety of different strategies are used by tumor cells to avoid recognition by different immune effector mechanisms. Among these escape routes, alteration of MHC class I cell surface expression is one of the mechanisms most widely used by tumor cells. In this review we focus our attention on the T-cell immune selection of MHC class I–deficient tumor variants. Different altered MHC class I phenotypes that originate from multiple molecular mechanisms can be identified in human tumors. MHC-deficient tumor clones can escape T-cell immune responses, but are in theory more susceptible to NK-cell–mediated lysis. In this context, we also review the controversial issue of the aberrant expression of nonclassical HLA class I molecules, particularly HLA-G, in tumors. This expression may be relevant in tumor cells that have lost the capacity to interact with NK inhibitory receptors—namely, those tumor cells with no HLA-B or HLA-C expression. Most published studies have not analyzed these possibilities and do not provide information about the complete HLA-A, HLA-B, or HLA-C molecule profiles of the tumors studied. In contrast, HLA-E has been reported to be expressed in some tumor cell lines with very low HLA-A, HLA-B, and HLA-C expression, suggesting that HLA-E may indeed, in some cases, play a role by inhibiting NK lysis of cells that otherwise would be destroyed by NK cells. Finally, we provide evidence that the status of the immune system in the tumor-bearing animal is capable of defining the MHC profile of the tumor cells. In other words, MHC class I–negative metastatic colonies are produced in immunocompetent animals, and MHC class I–positive colonies in T-cell immunodeficient individuals.This article forms part of the Symposium in Writing Tumor escape from the immune response, published in Vol. 53. 相似文献
6.
Alhamdani MS Youns M Buchholz M Gress TM Beckers MC Maréchal D Bauer A Schröder C Hoheisel JD 《Journal of Proteomics》2012,75(12):3747-3759
Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers, with a mortality that is almost identical to incidence. The inability to predict, detect or diagnose the disease early and its resistance to all current treatment modalities but surgery are the prime challenges to changing the devastating prognosis. Also, relatively little is known about pancreatic carcinogenesis. In order to better understand relevant aspects of pathophysiology, differentiation, and transformation, we analysed the cellular proteomes of 24 pancreatic cancer cell lines and two controls using an antibody microarray that targets 741 cancer-related proteins. In this analysis, 72 distinct disease marker proteins were identified that had not been described before. Additionally, categorizing cancer cells in accordance to their original location (primary tumour, liver metastases, or ascites) was made possible. A comparison of the cells' degree of differentiation (well, moderately, or poorly differentiated) resulted in unique marker sets of high relevance. Last, 187 proteins were differentially expressed in primary versus metastatic cancer cells, of which the majority is functionally related to cellular movement. 相似文献
7.
Immunological properties of a single-chain fragment of the anti-idiotypic antibody ACA125 总被引:6,自引:0,他引:6
Reinartz S Wagner U Giffels P Gruenn U Schlebusch H Wallwiener D 《Cancer immunology, immunotherapy : CII》2000,49(4-5):186-192
Vaccination with anti-idiotypic antibodies has been described as a promising concept for treatment of several malignant diseases.
The murine monoclonal anti-idiotypic antibody ACA125 imitates a specific epitope of the tumor-associated antigen CA125 expressed
by 80% of ovarian carcinomas. In the first clinical trial it could be shown that mAb ACA125 is able to elicit anti-anti-idiotypic
antibodies (Ab3) with anti-CA125 specificity in patients with advanced ovarian cancer. In order to improve the capabilities
of anti-idiotype vaccines we generated a genetically engineered single-chain fragment (scFv) ACA125 composed of heavy- and
light-chain variable regions connected by a flexible linker. The antigenicity of scFv ACA125 was demonstrated by immunizing
rats i.p. with scFv or complete mAb in complete/incomplete Freund's adjuvants (CFA/IFA) or precipitated by aluminium hydroxide.
Negative control groups included applications of irrelevant mouse IgG or adjuvants alone. Anti-anti-idiotypic antibodies (Ab3)
directed against the mAb ACA125 as well as specific anti-CA125 antibodies (Ab1′) could be detected in all animals treated
with scFv in CFA/IFA. Nevertheless, antibody titers were lower than when the complete mAb ACA125 was used. Suprisingly, an
increase of specificity could not be observed in scFv-immunized animals, which had been expected because of the lack of heavy-
and light-chain constant regions that could raise rather unspecific anti-isotypic and anti-allotypic rat anti-(mouse Ig) antibodies
(RAMA). In contrast, the RAMA responses detected in these rats were even stronger than those following immunization with complete
mAb ACA125. In conclusion, the anti-idiotypic scFv ACA125 alone cannot improve the immunogenic features of the corresponding
mAb, but provides a useful tool for the further development of genetic vaccines.
Received: 20 January 2000 / Accepted: 24 April 2000 相似文献
8.
Méndez R Rodríguez T Del Campo A Monge E Maleno I Aptsiauri N Jiménez P Pedrinaci S Pawelec G Ruiz-Cabello F Garrido F 《Cancer immunology, immunotherapy : CII》2008,57(5):719-729
Background Altered HLA class I cell surface expression is one of the major mechanisms by which tumor cells escape from T lymphocytes.
Immunohistochemistry-defined phenotypes of lost HLA class I expression have been described in human solid tumors, nut less
information is available on melanoma cell lines.
Objectives To describe the frequency and distribution of different types of HLA class I antigen alterations in 91 melanoma cell lines
from the European Searchable Tumour Cell and Databank (ESTDAB).
Methods The HLA class I expression was assessed by flow cytometry and HLA genotyping.
Results We found various types of HLA class I cell surface alterations in about 67% of the melanoma cell lines. These alterations
range from total to selective HLA class I loss due to loss of heterozygosity (LOH), haplotype loss, β2-microglobulin gene
mutation, and/or total or selective down-regulation of HLA class I molecules. The most frequently observed phenotype is down-regulation
of HLA-B locus that was reversible after treatment with IFN -γ.
Conclusions In general, HLA class I alterations in the majority of the cells analyzed were of regulatory nature and could be restored
by IFN-γ. Analysis of the frequency of distinct HLA class I altered phenotypes in these melanoma cell lines revealed specific
differences compared to other types of tumors.
Rosa Méndez and Teresa Rodríguez have equally contributed to this work and both should be considered as first authors. 相似文献
9.
Maureen P. Martin Anita Harding Robert Chadwick Mel Kronick Michael Cullen Ling Lin Emmanuel Mignot M. Carrington 《Immunogenetics》1997,47(2):131-138
The human genome contains a large number of interspersed microsatellite repeats which exhibit a high degree of polymorphism
and are inherited in a Mendelian fashion, making them extremely useful genetic markers. Several microsatellites have been
described in the HLA region, but allele nomenclature, a set of broadly distributed controls, and typing methods have not been standardized, which
has resulted in discrepant microsatellite data between laboratories. In this report we present a detailed protocol for genotyping
microsatellites using a semi-automated fluorescence-based method. Twelve microsatellites within or near the major histocompatibility
complex (MHC) were typed in the 10th International Histocompatibility Workshop homozygous typing cell lines (HTCs) and alleles
were designated based on size. All loci were sequenced in two HTCs providing some information on the level of complexity of
the repeat sequence. A comparison of allele size obtained by genotyping versus that obtained by direct sequencing showed minor
discrepancies in some cases, but these were not unexpected given the technical differences in the methodologies. Fluorescence-based
typing of microsatellites in the MHC described herein is highly efficient, accurate, and reproducible, and will allow comparison
of results between laboratories.
Received: 10 May 1997 / Revised: 1 August 1997 相似文献
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Ki Hyung Kim Yun-Jeong Kang Jin-Ok Jo Mee Sun Ock Soo Hyun Moon Dong Soo Suh Man Soo Yoon Eun-Sil Park Namkung Jeong Wan-Kyu Eo Heung Yeol Kim Hee-Jae Cha 《Biochemical and biophysical research communications》2014
DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. 相似文献
14.
Dae Kyoung Kim Min Hee Ham Seo Yul Lee Min Joo Shin Ye Eun Kim Parkyong Song Dong-Soo Suh Jae Ho Kim 《BMB reports》2020,53(12):622
Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anti-cancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer. 相似文献
15.
Joint Report of the First International Comparison Test on Swine Lymphocyte Alloantigens (SLA) 总被引:5,自引:0,他引:5
CH. RENARD B. KRISTENSEN C. GAUTSCHI V. HRUBAN M. FREDHOLM M. VAIMAN 《Animal genetics》1988,19(1):63-72
The first international comparison test on swine lymphocyte alloantigens (SLA) was held in Helsinki, Finland in July 1986. The results reported were based on a comparison of 157 alloantisera originating from six laboratories. The antisera were tested against a selected panel of 264 lymphocyte samples belonging to four laboratories. The most common breeds in Europe were chosen for this first comparison test (Landrace and Large White). Eighteen of the 31 previously known specificities were confirmed and a new nomenclature was established. 相似文献
16.
Glen R. Guerra Joseph C. Kong Rosemary M. Millen Matthew Read David S. Liu Sara Roth Shienny Sampurno Joseph Sia Maria-Pia Bernardi Timothy J. Chittleborough Corina C. Behrenbruch Jiasian Teh Huiling Xu Nicole M. Haynes Jiaan Yu Richard Lupat David Hawkes Natasha Di Costanzo Richard W. Tothill Catherine Mitchell Samuel Y. Ngan Alexander G. Heriot Robert G. Ramsay Wayne A. Phillips 《Cell death & disease》2021,12(11)
Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.Subject terms: Targeted therapies, Anal cancer, Immune evasion, Cancer models 相似文献
17.
R. K. Saxena Q. B. Saxena T. L. Whiteside R. H. Goldfarb R. B. Herberman 《Journal of biosciences》1996,21(1):13-25
A cytokine which augments the expression of major histocompatibility complex (MHC) I antigens on K562 and gastric carcinoma
tumour (HR) cells, has been isolated from the culture supernatant of Concanavalin-A (Con-A) activated human peripheral blood
mononuclear cells. The factor, termed MHC augmenting factor (MHC- AF) has been partially purified by Sephadex G- 100 column
chromatography, preparative isoelectric focusing and HPLC with ion- exchange as well as sizing columns. MHC-AF activity is
associated with a 35 kDa molecule which has pI of 6.0. Interferon (IFN)-α, \, tumour necrosis factor (TNF), Interleukin (IL)-2,
IL-4, IL-5 and IL-7 had no significant effect in MHC- AF bioassay, but IFN-γ had significant MHC-AF activity. Antibodies to
IFN-α, IFN-\ and TNF-α did not block the activity of MHC-AF, but anti-IFN-y antibodies could partially neutralize the activity.
However, unlike IFN-γ, MHC-AF activity was resistant to pH 2.0 treatment. Purified MHC-AF preparations did not have any activity
in WISH cell/encephalo myocarditis virus (EMC) IFN bioassays. In addition, anti-IFN-y affinity column did not retain MHC-AF
activity. These results indicate that a MHC-AF distinct from IFN-γ, is produced by activated human mononuclear cells. 相似文献
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Ovarian cancer is the deadliest gynecological malignancy. It is typically diagnosed at advanced stages of the disease, with metastatic sites disseminated widely within the abdominal cavity. Ovarian cancer treatment is challenging due to high disease recurrence and further complicated pursuant to acquired chemoresistance. Cancer stem cell(CSC) theory proposes that both tumor development and progression are driven by undifferentiated stem cells capable of self-renewal and tumor-initiation. The most recent evidence revealed that CSCs in terms of ovarian cancer are not only responsible for primary tumor growth, metastasis and relapse of disease, but also for the development of chemoresistance. As the elimination of this cell population is critical for increasing treatment success, a deeper understanding of ovarian CSCs pathobiology, including epithelial-mesenchymal transition, signaling pathways and tumor microenvironment, is needed. Finally, before introducing new therapeutic agents for ovarian cancer, targeting CSCs, accurate identification of different ovarian stem cell subpopulations, including the very small embryoniclike stem cells suggested as progenitors, is necessary. To these ends, reliable markers of ovarian CSCs should be identified. In this review, we present the current knowledge and a critical discussion concerning ovarian CSCs and their clinical role. 相似文献
19.
A Vigani L Miglietta S Chiara L Repetto E Pichi G Cimoli L Morelli L Poggi G Billi S Parodi 《Bollettino della Società italiana di biologia sperimentale》1990,66(6):537-542
Ovarian cancer is the second most common gynecologic malignancy. Standard therapeutic approaches to this disease, surgery followed by chemotherapy, have produced response rates of up to 80%. However, the five-year survival rate remains around 30%. Recently, Tumor Necrosis Factor (TNF) has received attention as either an alternative or an associated agent for chemotherapy of ovarian cancer. TNF is known to have direct cytotoxic and cytostatic effects on a variety of transformed cell lines "in vitro". Furthermore, TNF is known to enhance significantly the "in vitro" effects of a class of chemotherapeutic agents, specifically those targeted at DNA topoisomerase II. In this work we have investigated TNF-induced cytotoxicity in four established human epithelial ovarian cancer cell lines: A-2774; SV-626; SKOV-3 and Pa-1. TNF mediated cytotoxic activity was observed in a range of concentrations between 1 U/ml and 10-3 U/ml. A-2774 and SV-626 were the two most sensitive lines, especially when exposed to high concentrations of TNF. 相似文献
20.
Our previous study described a real-time PCR method to quantify microRNA (miRNA) precursors using SYBR green detection [T. D. Schmittgen, J. Jiang, Q. Liu and L. Yang (2004) Nucleic Acids Res., 32, e43]. The present study adapted the assay to a 384-well format and expanded it to include primers to 222 human miRNA precursors. TaqMan minor groove binder probes were used to discriminate nearly identical members of the let-7 family of miRNA isoforms. The miRNA precursor expression was profiled in 32 human cell lines from lung, breast, colorectal, hematologic, prostate, pancreatic, and head and neck cancers. Some miRNA precursors were expressed at similar levels in many of the cell lines, while others were differentially expressed. Clustering analysis of the miRNA precursor expression data revealed that most of the cell lines clustered into their respective tissues from which each cell line was ostensibly derived. miRNA precursor expression by PCR paralleled the mature miRNA expression by northern blotting for most of the conditions studied. Our study provides PCR primer sequences to all of the known human miRNA precursors as of December 2004 and provides a database of the miRNA precursor expression in many commonly used human cancer cell lines. 相似文献