Abstract：
:The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses by trimming peptides for presentation by MHC class I (MHC-I) molecules. Herein, we demonstrate that genetic or pharmacological inhibition of ERAP1 on human tumor cell lines perturbs their ability to engage several classes of inhibitory receptors by their specific ligands, including killer cell Ig-like receptors (KIR) by classical MHC-I-peptide (pMHC-I) complexes and the lectin-like receptor CD94-NKG2A by nonclassical pMHC-I complexes, in each case leading to natural killer (NK) cell killing. The protective effect of pMHC-I complexes could be restored in ERAP1-deficient settings by the addition of known high-affinity peptides, suggesting that ERAP1 was needed to positively modify the affinity of natural ligands. Notably, ERAP1 inhibition enhanced the ability of NK cells to kill freshly established human lymphoblastoid cell lines from autologous or allogeneic sources, thereby promoting NK cytotoxic activity against target cells that would not be expected because of KIR-KIR ligand matching. Overall, our results identify ERAP1 as a modifier to leverage immune functions that may improve the efficacy of NK cell-based approaches for cancer immunotherapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Cifaldi L,Romania P,Falco M,Lorenzi S,Meazza R,Petrini S,Andreani M,Pende D,Locatelli F,Fruci Ddoi
10.1158/0008-5472.CAN-14-1643subject
Has Abstractpub_date
2015-03-01 00:00:00pages
824-34issue
5eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-14-1643journal_volume
75pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:In vitro cell-mediated cytotoxicity (CMC) assays have been carried out in human melanoma system with blood effector lymphocytes on [3H]proline-labeled target cells in a 48-hr microcytotoxicity technique. Three lymphocyte purification procedures (Ficoll:Hypaque gradient, plasma gel sedimentation followed by nylon colum...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-12-01 00:00:00
abstract：:The Notch ligand delta-like 4 (Dll4) has been identified as a promising target in tumor angiogenesis in preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. In this study, we report the development of REGN421 (enoticumab), a fully human IgG1 monocl...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3773
更新日期：2015-10-01 00:00:00
abstract：:Obesity is associated with increased cancer incidence and mortality. We have previously found that obesity in children is associated with a 50% increased recurrence of acute lymphoblastic leukemia (ALL) in high-risk patients. We have therefore developed novel in vivo and in vitro preclinical models to study the mechan...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-0800
更新日期：2009-10-01 00:00:00
abstract：:SUMO-1 conjugation modulates numerous cellular functions, including the subnuclear localization of its target proteins. The WT1 tumor suppressor encodes a four-zinc finger protein with distinct splicing isoforms. WT1(-KTS), encoding uninterrupted zinc fingers, functions as a transcription factor and has a diffusely nu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-1502
更新日期：2004-11-01 00:00:00
abstract：:The retinoblastoma (Rb) family consists of the tumor suppressor pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies of the retinoblastoma family of proteins in 235 specimens of lung cancer show the tightest inverse association between the histological grading in the most aggressive tum...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-01-15 00:00:00
abstract：:In the present study, we examined hemodynamics in vasculogenic mimicry (VM) and angiogenesis of inflammatory breast cancer (IBC) xenografts (WIBC-9), having previously reported on the unique histological features and molecular basis of these processes (K. Shirakawa et al., Cancer Res., 61: 445-451, 2001). Histological...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-01-15 00:00:00
abstract：:Adaptive therapy seeks to exploit intra-tumoral competition to avoid, or at least delay, the emergence of therapy resistance in cancer. Motivated by promising results in prostate cancer, there is growing interest in extending this approach to other neoplasms. As such, it is urgent to understand the characteristics of ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-20-0806
更新日期：2020-11-10 00:00:00
abstract：:The inactivation of the tumor suppressor gene p53 has been demonstrated in a variety of human tumors. In this study, we present a p53 gene analysis of 13 uterine carcinoma cell lines. Sequencing analysis of the entire coding region revealed mutations changing the p53 amino acid composition in all six endometrial carci...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-12-15 00:00:00
abstract：:The effects of the lipid-soluble dihydrofolate reductase inhibitor, trimetrexate, on the inhibition of thymidylate biosynthesis as a result of perturbation in cellular folate pools in H35 hepatoma cells in vitro has been investigated. Exposure of the cultures to increasing concentrations of trimetrexate between 2 and ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:cis-Diammine(1,1-cyclobutanedicarboxylato)platinum (CBDCA) is a nonnephrotoxic but myelosuppressive analogue of cisplatin (DDP) with greatly reduced protein binding and greatly increased renal excretion. Thus, CBDCA might produce undue toxicity in patients with decreased renal function. Twenty-two patients [14 females...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:Paclitaxel has been shown to activate Raf-1 and cause phosphorylation of Bcl-2, which has been correlated with paclitaxel-induced apoptosis of cancer cells. In the present studies, we demonstrate that in human AML HL-60 cells that express Bcl-2 but little Bcl-xL (HL-60/neo cells), paclitaxel-induced phosphorylation of...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-03-15 00:00:00
abstract：:Mouse myeloma cells were fused with spleen cells from BALB/c mice immunized with a cell line derived from human small cell carcinoma (SCC) of the lung. The cloned hybridoma SM1 produced antibody that was reactive with the surface membrane of SCC cell lines and SCC tumors but not with the membrane of several non-SCC ce...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:Carcinomas of the exocrine pancreas are poorly understood and have a poor prognosis because of their highly malignant nature. Using two human pancreatic cancer cell lines, AsPc-1 and Capan-2, we have investigated avenues that might be useful in targeting the delivery of antineoplastic agents to such cancers. Qualitati...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:In an effort to achieve high concentrations of 5-fluorouracil (5-FUra) in the hepatic circulation while minimizing systemic exposure, several routes of intrahepatic administration were compared in the canine model. To ascertain these data, 5-FUra (30 mg/kg) was given as a bolus into either a systemic vein (femoral vei...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:The prevalence, size, and patterns of distribution of arterial lesions (plaques) were investigated in cockerels exposed chronically to 7,12-dimethylbenz(a)anthracene (DMBA). Animals, from 5 to 20 weeks of age, received weekly i.m. injections of 5, 10, or 20 mg of DMBA per kg, dissolved in dimethyl sulfoxide. Control a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:Whole-genome sequencing studies have recently identified a quarter of cases of the rare childhood brainstem tumor diffuse intrinsic pontine glioma to harbor somatic mutations in ACVR1. This gene encodes the type I bone morphogenic protein receptor ALK2, with the residues affected identical to those that, when mutated ...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-14-1298
更新日期：2014-09-01 00:00:00
abstract：:Molecular markers of pancreatic neoplasia could aid in the evaluation of visible pancreatic lesions and indicate neoplasia invisible to imaging. We evaluated methylation-specific PCR (MSP) assays that detect aberrantly methylated DNA for their use as markers of pancreatic neoplasia. Methylation analysis was done on pa...
journal_title：Cancer research
pub_type： 临床试验,杂志文章
doi：10.1158/0008-5472.CAN-05-2664
更新日期：2006-01-15 00:00:00
abstract：:To sustain their proliferation, cancer cells become dependent on one-carbon metabolism to support purine and thymidylate synthesis. Indeed, one of the most highly upregulated enzymes during neoplastic transformation is MTHFD2, a mitochondrial methylenetetrahydrofolate dehydrogenase and cyclohydrolase involved in one-c...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-1476
更新日期：2017-02-15 00:00:00
abstract：:Transduction of malignant cells with toxin genes provides a novel means to promote tumor cell destruction. The efficacy of a toxin gene is dependent on the cell type targeted, the quantity of exogenous protein synthesized, and the mechanisms of growth inhibition and bystander killing. To develop gene therapy for targe...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-03-15 00:00:00
abstract：:The objective of this study was to investigate the induction of liver tumors by arylhydroxamic acids. The potential involvement of sulfate conjugation was minimized by the administration of a N-hydroxy-4-acylaminobiphenyl to female CD rats. This experimental design provided for the exposure of a target organ that has ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-06-01 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) has been investigated as a potent mediator of brain tumor angiogenesis, vascular permeability, and glioma growth. Using a VEGF ELISA, we determined the concentration of VEGF in the sera and tumor extracts of 19 brain tumor patients including glioblastoma, anaplastic astrocytom...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:Recombinant immunotoxins (RIT) have been highly successful in cancer therapy due, in part, to the high cancer-specific expression of cell surface antigens such as mesothelin, which is overexpressed in mesothelioma, ovarian, lung, breast, and pancreatic cancers, but is limited in normal cells. RG7787 is a clinically op...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-2401
更新日期：2016-03-15 00:00:00
abstract：:Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors and cyclooxygenase-1 (COX-1) is now being reconsidered as a target for chemoprevention. Our aims were to determine whether selective COX-1 inhibition could delay or prevent cancer development a...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-2245
更新日期：2014-01-01 00:00:00
abstract：:BALB/cJ X C57BL/10Sn F1 (hereafter called B10F1) hybrids resist challenge with the BALB/c plasmacytoma, MPC-11, by a radiation-sensitive, silica-insensitive mechanism, whereas BALB/cJ X BALB.B F1 (hereafter called BALB.BF1) hybrids are as susceptible to MPC-11 as are homozygous BALB/c mice themselves. To investigate t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:Cancer stem-like cells (CSC) in hepatocellular carcinoma (HCC) are thought to mediate therapeutic resistance and poor survival outcomes, but their intrinsic and extrinsic control is not well understood. In this study, we found that the chromatin modification factor LSD1 is highly expressed in HCC CSC where it decrease...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-1236
更新日期：2018-02-15 00:00:00
abstract：:Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1883
更新日期：2011-12-01 00:00:00
abstract：:A direct ligand-banding radioassay for methotrexate (MTX) has been developed using dihydrofolate reductase, contained in the lysate of L1210 leukemia cells, as the binding determinant. The procedure is a two-phase reaction system where standard MTX concentrations or the sample being assayed in incubated with the reage...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-08-01 00:00:00
abstract：:Tissues from 22 patients with glioma and 7 patients with normal white matter were used in this study. First we determined the proliferating area in the tumor tissue by evaluating the growth fraction (GF). Second we determined the mean number of cells and measured the intercapillary distance in a modified tumor cord in...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-05-15 00:00:00
abstract：:Possible mechanisms whereby alcohol abuse and alcohol-related diseases may promote the development of cancer are analyzed. The mechanisms discussed include: (a) contact-related local effects on the upper gastrointestinal tract; (b) the presence of low levels of carcinogens in alcoholic beverages; (c) induction of micr...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：
更新日期：1979-07-01 00:00:00
abstract：:Activity increase of the cytosolic isozyme of thymidine kinase (TK) in resected specimens of lung tumor patients would be a useful marker for tumor malignancy and prognosis. In 24 resected cases of malignant lung tumors, the whole enzyme extracts of the tumorous part of the specimens showed that the activities of TK, ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
