Abstract:
:Plasmacytoid dendritic cells (pDC) are the main producers of a key T-cell-stimulatory cytokine, IFNα, and critical regulators of antiviral immunity. Chronic myeloid leukemia (CML) is caused by BCR-ABL, which is an oncogenic tyrosine kinase that can be effectively inhibited with ABL-selective tyrosine kinase inhibitors (TKI). BCR-ABL-induced suppression of the transcription factor interferon regulatory factor 8 was previously proposed to block pDC development and compromise immune surveillance in CML. Here, we demonstrate that pDCs in newly diagnosed CML (CML-pDC) develop quantitatively normal and are frequently positive for the costimulatory antigen CD86. They originate from low-level BCR-ABL-expressing precursors. CML-pDCs also retain their competence to maturate and to secrete IFN. RNA sequencing reveals a strong inflammatory gene expression signature in CML-pDCs. Patients with high CML-pDC counts at diagnosis achieve inferior rates of deep molecular remission (MR) under nilotinib, unless nilotinib therapy is combined with IFN, which strongly suppresses circulating pDC counts. Although most pDCs are BCR-ABL-negative in MR, a substantial proportion of BCR-ABL+ CML-pDCs persists under TKI treatment. This could be of relevance, because CML-pDCs elicit CD8+ T cells, which protect wild-type mice from CML. Together, pDCs are identified as novel functional DC population in CML, regulating antileukemic immunity and treatment outcome in CML.Significance: CML-pDC originates from low-level BCR-ABL expressing stem cells into a functional immunogenic DC-population regulating antileukemic immunity and treatment outcome in CML. Cancer Res; 78(21); 6223-34. ©2018 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Inselmann S,Wang Y,Saussele S,Fritz L,Schütz C,Huber M,Liebler S,Ernst T,Cai D,Botschek S,Brendel C,Calogero RA,Pavlinic D,Benes V,Liu ET,Neubauer A,Hochhaus A,Burchert Adoi
10.1158/0008-5472.CAN-18-1477subject
Has Abstractpub_date
2018-11-01 00:00:00pages
6223-6234issue
21eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-18-1477journal_volume
78pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against breast cancer but biochemical mechanisms are unclear. Our studies showed that the n-3 fatty acid docosahexaenoic acid (DHA) up-regulated syndecan-1 (SDC-1) in human breast cancer cells, and we tested the hypothesis that DHA-mediated up-re...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2305
更新日期:2008-04-15 00:00:00
abstract::Sixty % of clones isolated from HeLa cells treated with toxic concentrations of a methylating carcinogen showed increased resistance to the cytotoxicity of N-methyl-N-nitrosourea. D37 values were 6- to 100-fold higher than in the parental cell population. The absence of detectable levels of the repair enzyme O6-methyl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-06-15 00:00:00
abstract::Quinocarmycin monicitrate (KW2152) and its analogue, DX-52-1, demonstrated specificity for melanomas in the National Cancer Institute in vitro human tumor cell line drug screen. In contrast to most cell lines, a 50% reduction in tumor cell burden (as measured protein) at the end of a 48-h drug incubation was produced ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-15 00:00:00
abstract::A deletion in an Alu repetitive sequence in the fifth intron of the c-sis gene of meningioma patients was previously described (M. Smidt et al., J. Clin. Invest., 86:1151-1157, 1990). The authors analyzed the structure of this intron in DNA from peripheral blood leukocytes and tumor samples of 86 patients with sporadi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-08-15 00:00:00
abstract::Gene therapy strategies for cancer currently aim at targeting gene delivery to the malignant cell. In a mouse model of intracerebral Lewis lung carcinoma (3LL), adenoviral vectors transduce not only 3LL cells but also brain parenchymal cells including endothelial cells, neurons, microglia, and astrocytes in vivo. Furt...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
abstract::We performed parallel array comparative genomic hybridization and array expression analysis of the 12p11-p12 amplicon in human testicular seminomas and an ovarian carcinoma cell line using an expressed sequence tags (ESTs) array spotted with 8254 ESTs. The data were normalized using a robust statistical modeling and t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
abstract::A transplantable bladder tumor (Chapman R-4909) of the rat, when first received in our laboratory, grew with a complex histopathology. The predominant component was transitional cell carcinoma, but there were foci of keratinization, including pearl formation, and foci of a less well-defined cystic appearance. We repor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::Cell signaling plays a central role in the etiology of cancer. Numerous therapeutics in use or under development target signaling proteins; however, off-target effects often limit assignment of positive clinical response to the intended target. As direct measurements of signaling protein activity are not generally fea...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1709
更新日期:2009-12-01 00:00:00
abstract::The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal the...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-3313
更新日期:2017-11-01 00:00:00
abstract::Unambiguous and sensitive methods based on gas chromatography-chemical ionization mass spectrometry have been developed to quantitate cyclophosphamide and two alkylating and cytotoxic metabolites, phosphoramide mustard and nornitrogen mustard. The levels of these materials have been determined in the plasma and urine ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-02-01 00:00:00
abstract::Cancer chemotherapy may be improved by increasing antineoplastic drug specificity for tumor cells. We have synthesized a glucuronide prodrug that can be enzymatically converted to an antineoplastic agent at tumor cells that are able to bind beta-glucuronidase-monoclonal antibody conjugates. The glucuronide prodrug BHA...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-08-15 00:00:00
abstract::Studies demonstrate that some colon cancers possess receptors for various gastrointestinal hormones or neurotransmitters, the occupation of which can affect growth. These results are limited because frequently only a small number of tumors are studied, only 1 or 2 receptors are sought, and the effect on cell function ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Organic anion transporting polypeptide 1B3 (OATP1B3, SLCO1B3) is normally expressed in hepatocytes. In this study, we showed frequent overexpression of OATP1B3 in colorectal adenocarcinomas. Quantitative reverse transcription-PCR analysis of 17 colon tumors indicated tumoral overexpression of OATP1B3 by approximately ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1984
更新日期:2008-12-15 00:00:00
abstract::Twenty-eight patients with metastatic malignant melanoma received anti-p97 murine monoclonal antibody (96.5) infused over 2 h at doses between 1 and 20 mg coupled to either 2.5 or 5.0 mCi of 111In by the bifunctional chelating agent diethyltriaminepentaacetic acid. Clearance of 111In from plasma closely fit an open, o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::Low oxygen levels have been shown to promote self-renewal in many stem cells. In tumors, hypoxia is associated with aggressive disease course and poor clinical outcomes. Furthermore, many aggressive tumors have been shown to display gene expression signatures characteristic of human embryonic stem cells (hESC). We now...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-3320
更新日期:2011-07-01 00:00:00
abstract::The discovery of oncogenic driver mutations and the subsequent developments in targeted therapies have led to improved outcomes for subsets of lung cancer patients. The identification of additional oncogenic and drug-sensitive alterations may similarly lead to new therapeutic approaches for lung cancer. We identify an...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-3771
更新日期:2015-08-01 00:00:00
abstract::The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications in tumorigenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancer. Restoration of SFRP function attenuates Wnt signaling and induces apoptosis in a variety of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2005-02-01 00:00:00
abstract::The conditions for growing preneoplastic mammary epithelial cells in primary cell cultures with serum-free factor-defined medium were established in a series of experiments. The cells, grown in Dulbecco's modified Eagle's medium with 0.6 mM Ca2+, epidermal growth factor, transferrin, insulin, and Na2SeO3, were fibrobl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract::2-Phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) is classified as a relatively nontoxic selenium compound, probably because of its bound selenium moiety. In thiol-rich tissues, such as the kidneys, ebselen is converted into selenol intermediates. Selenols are nucleophilic agents which might be able to react with plat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract::p16Ink4 and p15Ink4B are cyclin-dependent kinase 4 inhibitors and link to the regulation of cell cycle in mammalian cells. The genes encoding these inhibitors are located at 9p21, which is a frequent site of allelic loss in various types of tumors. Twenty-five primary biliary tract cancers were examined for somatic mu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::Telomerase is a ribonucleoprotein that synthesizes telomeric DNA on chromosomal ends. Telomerase activation has been seen in many immortal cell lines and cancers. Telomerase activity was analyzed in prostate carcinoma; in coexistent prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), atrophy...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-02-15 00:00:00
abstract::We examined the genetic requirements for the Myc family of oncogenes in normal Sonic hedgehog (Shh)-mediated cerebellar granule neuronal precursor (GNP) expansion and in Shh pathway-induced medulloblastoma formation. In GNP-enriched cultures derived from N-myc(Fl/Fl) and c-myc(Fl/Fl) mice, disruption of N-myc, but not...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1621
更新日期:2006-09-01 00:00:00
abstract::Cholangiocarcinoma is a strongly aggressive malignancy with a very poor prognosis. Effective therapeutic strategies are lacking because molecular mechanisms regulating cholangiocarcinoma cell growth are unknown. Furthermore, experimental in vivo animal models useful to study the pathophysiologic mechanisms of malignan...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6682
更新日期:2008-08-15 00:00:00
abstract::Expression of cyclooxygenase (COX)-2 protein in 4-nitroquinoline-1-oxide (4-NQO)-induced rat tongue lesions and the postinitiation chemopreventive potential of a selective COX-2 inhibitor, nimesulide (NIM), were examined in Fischer 344 male rats. NIM was administered in the diet at doses of 150, 300, and 600 ppm for 1...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-02-15 00:00:00
abstract::We conjugated the chemotherapy agent daunorubicin to the anti-T-cell monoclonal antibody T101 using an active ester intermediate of the acid-labile linker cis-aconitate anhydride. By converting carbohydrate hydroxyl groups on the antibody to amines prior to conjugation, average drug to antibody ratios of 25:1 were ach...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
abstract::Homogeneously staining regions (HSRs) were found in hypodiploid cells (40%) of a subline of the human melanoma cell line, MeWo, (MeWo-C) but were absent from the hypotetraploid cells (60%). Another subline (MeWo-B) was also shown to contain two populations of cells, 70% hypodiploid and 30% hypotetraploid. None of the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Ether phospholipids are analogues of the naturally occurring 2-lyso-phosphatidylcholine that have been reported to have in vitro/in vivo antitumor activity. Their antiproliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of two ether p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::5-iododeoxyuridine (IdUrd) is highly effective in inducing the production of endogenous viruses (e.g., RNA-containing murine leukemia virus) from a variety of cell lines that normally do not release such viruses. For the activation of murine leukemia virus by IdUrd, its incorporation into cellular DNA is necessary. We...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-05-01 00:00:00
abstract::Dormancy in the murine BCL1 lymphoma can be induced by several strategies including cytoreductive therapy of mice with large tumor burdens and challenge of allogeneic chimeric mice or idiotype-immunized mice with BCL1 tumor. Dormant tumor cells were isolated from the spleens of the chimeric mice and the majority were ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-09-15 00:00:00
abstract::Protein kinases of the Raf family act as signal-transducing elements downstream of activated cell surface receptors and are involved in the regulation of proliferation, differentiation, and cell survival. Whereas the role of c-Raf-1 as a mitogen-activated protein/extracellular signal-regulated kinase activator within ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-07-15 00:00:00