Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens.

Abstract:

:Leukemic stem cells (LSC) might be the source for leukemic disease self-renewal and account for disease relapse after treatment, which makes them a critical target for further therapeutic options. We investigated the role of cytotoxic T-lymphocytes (CTL) counteracting and recognizing LSC. Leukemia-associated antigens (LAA) represent immunogenic structures to target LSC. We enriched the LSC-containing fraction of 20 AML patients and hematopoietic stem cells (HSC) of healthy volunteers. Using microarray analysis and qRT-PCR we detected high expression of several LAA in AML cells but also in LSC. PRAME (p = 0.0085), RHAMM (p = 0.03), WT1 (p = 0.04) and Proteinase 3 (p = 0.04) showed significant differential expression in LSC compared with HSC. PRAME, RHAMM and WT1 are furthermore also lower expressed on leukemic bulk. In contrast, Proteinase 3 indicates a higher expression on leukemic bulk than on LSC. In colony forming unit (CFU) immunoassays, T cells stimulated against various LAA indicated a significant inhibition of CFUs in AML patient samples. The LAA PRAME, RHAMM and WT1 showed highest immunogenic responses with a range up to 58-83%. In a proof of principle xenotransplant mouse model, PRAME-stimulated CTL targeted AML stem cells, reflected by a delayed engraftment of leukemia (p = 0.0159). Taken together, we demonstrated the expression of several LAA in LSC. LAA-specific T cells are able to hamper LSC in immunoassays and in a mouse model, which suggests that immunotherapeutic approaches have the potential to target malignant stem cells.

journal_name

Int J Cancer

authors

Schneider V,Zhang L,Rojewski M,Fekete N,Schrezenmeier H,Erle A,Bullinger L,Hofmann S,Götz M,Döhner K,Ihme S,Döhner H,Buske C,Feuring-Buske M,Greiner J

doi

10.1002/ijc.29583

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

2083-92

issue

9

eissn

0020-7136

issn

1097-0215

journal_volume

137

pub_type

杂志文章
  • HMFG1 antigen: a new marker for carcinomatous meningitis.

    abstract::Carcinomatous meningitis is a devastating metastatic complication of systemic carcinoma, which may occur insidiously, accompanied by a confusing spectrum of clinical symptoms and signs. In the absence of reliable diagnostic tumour markers, the diagnosis is established by the demonstration of malignant cells within the...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910440310

    authors: Moseley RP,Oge K,Shafqat S,Moseley CM,Sullivan NM,Badley RA,Burchell J,Taylor-Papadimitriou J,Coakham HB

    更新日期:1989-09-15 00:00:00

  • Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study.

    abstract::Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using 2 measures of acrylamide exposure: intake from ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24175

    authors: Wilson KM,Bälter K,Adami HO,Grönberg H,Vikström AC,Paulsson B,Törnqvist M,Mucci LA

    更新日期:2009-05-15 00:00:00

  • Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome.

    abstract::The aim of this study was to identify pathways that have a significant impact during renal carcinogenesis. Sixty-seven paired samples of both noncancerous renal cortex tissue and cancerous tissue from patients with clear cell renal cell carcinomas (RCCs) were subjected to whole-exome, methylome and transcriptome analy...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.28768

    authors: Arai E,Sakamoto H,Ichikawa H,Totsuka H,Chiku S,Gotoh M,Mori T,Nakatani T,Ohnami S,Nakagawa T,Fujimoto H,Wang L,Aburatani H,Yoshida T,Kanai Y

    更新日期:2014-09-15 00:00:00

  • A novel SOCS5/miR-18/miR-25 axis promotes tumorigenesis in liver cancer.

    abstract::The role of miRNAs with tumor suppressive activity in liver cancer has been well studied. However, little is known about potential oncomiRs in HCC. In our study, we conducted a systematic evaluation of candidate oncomiRs and found that upregulation of miR-18a and miR-25 in HCC was associated with poor patient survival...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31857

    authors: Sanchez-Mejias A,Kwon J,Chew XH,Siemens A,Sohn HS,Jing G,Zhang B,Yang H,Tay Y

    更新日期:2019-01-15 00:00:00

  • Novel approach for detecting global epigenetic alterations associated with tumor cell aneuploidy.

    abstract::Although aneuploidy is commonly observed in human cancers, the molecular mechanism underlying aneuploidization remains unclear. We used multiploid cancer model that had diploid and aneuploid cancer cells within the same cancerous tissue and attempted to detect specific epigenetic alterations associated with tumor cell...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22847

    authors: Habano W,Sugai T,Jiao YF,Nakamura S

    更新日期:2007-10-01 00:00:00

  • Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases.

    abstract::A human cancer vaccine composed of autologous tumor cells modified with the hapten dinitrofluorobenzene (DNP) induces cell-mediated immunity to the tumor cells and the development of inflammatory responses within metastatic sites. In this study we determined whether DNP vaccine could induce regression of established m...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.1506.abs

    authors: Berd D,Sato T,Cohn H,Maguire HC Jr,Mastrangelo MJ

    更新日期:2001-11-01 00:00:00

  • Association between breast cancer risk and disease aggressiveness: Characterizing underlying gene expression patterns.

    abstract::The association between breast cancer risk defined by the Tyrer-Cuzick score (TC) and disease prognosis is not well established. Here, we investigated the relationship between 5-year TC and disease aggressiveness and then characterized underlying molecular processes. In a case-only study (n = 2474), we studied the ass...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33270

    authors: Ugalde-Morales E,Grassmann F,Humphreys K,Li J,Eriksson M,Tobin NP,Borg Å,Vallon-Christersson J,Hall P,Czene K

    更新日期:2021-02-15 00:00:00

  • New pharmacological effect of fulvestrant to prevent oxaliplatin-induced neurodegeneration and mechanical allodynia in rats.

    abstract::Oxaliplatin, which is widely used as chemotherapy for certain solid cancers, frequently causes peripheral neuropathy. Commonly described neuropathic symptoms include aberrant sensations such as mechanical allodynia (hypersensitivity to normally innocuous stimuli). Although oxaliplatin neuropathy is a dose-limiting tox...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32043

    authors: Yamamoto S,Yamashita T,Ito M,Caaveiro JMM,Egashira N,Tozaki-Saitoh H,Tsuda M

    更新日期:2019-10-15 00:00:00

  • Epithelial phenotype as a predictive marker for response to EGFR-TKIs in non-small cell lung cancer patients with wild-type EGFR.

    abstract::Epithelial-to-mesenchymal transition (EMT) has profound impacts on cancer progression and also on drug resistance, including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Nowadays, there is still no predictive biomarker identified for the use of EGFR-TKIs in non-small cell lung cancer (NSCLC...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.28925

    authors: Ren S,Su C,Wang Z,Li J,Fan L,Li B,Li X,Zhao C,Wu C,Hou L,He Y,Gao G,Chen X,Ren J,Li A,Xu G,Zhou X,Zhou C,Schmid-Bindert G

    更新日期:2014-12-15 00:00:00

  • Two distinct regions of deletion on chromosome 13q in primary nasopharyngeal carcinoma.

    abstract::Nasopharyngeal carcinoma (NPC) is rare in most parts of the world, but prevalent in Southern China. Although this disease poses a serious health problem in our population, the genetic alterations that lead to the development of NPC have yet to be defined. In a comparative genomic hybridization (CGH) study on NPC by ou...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19991029)83:3<305::aid-ijc

    authors: Tsang YS,Lo KW,Leung SF,Choi PH,Fong Y,Lee JC,Huang DP

    更新日期:1999-10-29 00:00:00

  • Prevalence of antibody to adult T-cell leukemia virus-associated antigens (ATLA) in Japanese monkeys and other non-human primates.

    abstract::The prevalence of adult T-cell-leukemia virus (ATLV) infection was examined in Japanese monkeys living naturally in various parts of Japan and in other species of non-human primates imported into and kept in Japan. Sera of 2,650 Japanese monkeys from 41 troops throughout Japan were tested. High incidences of anti-ATLV...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910330205

    authors: Hayami M,Komuro A,Nozawa K,Shotake T,Ishikawa K,Yamamoto K,Ishida T,Honjo S,Hinuma Y

    更新日期:1984-02-15 00:00:00

  • Permissive expansion and homing of adoptively transferred T cells in tumor-bearing hosts.

    abstract::Activated T cells expressing endogenous or transduced TCRs are two cell types currently used in clinical adoptive T-cell therapy. The ability of these cells to recognize their antigen, expand and traffic to the tumor site are the initial steps necessary for successful therapy. In this study, we used in vivo biolumines...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29401

    authors: Perez C,Jukica A,Listopad JJ,Anders K,Kühl AA,Loddenkemper C,Blankenstein T,Charo J

    更新日期:2015-07-15 00:00:00

  • Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug-resistant colon carcinoma cells (LoVo) than on their wild-type counterparts.

    abstract::The occurrence of resistance to cytotoxic agents in tumor cells, associated with several phenotypic alterations, is one of the major obstacles to successful anticancer chemotherapy. A new strategy to overcome MDR of human cancer cells was studied, using BSAO, which generates cytotoxic products from spermine, H(2)O(2) ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10310

    authors: Calcabrini A,Arancia G,Marra M,Crateri P,Befani O,Martone A,Agostinelli E

    更新日期:2002-05-01 00:00:00

  • The presence of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells: their possible role in swainsonine-augmented human NK cytotoxicity.

    abstract::In the present study we examined the expression of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells and investigated their possible role in the human NK-cell phenomenon. The incubation of either peripheral-blood lymphocytes (PBL) or large granular lymphocytes (LGL) with swainsonine (S...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910520428

    authors: Yagita M,Noda I,Maehara M,Fujieda S,Inoue Y,Hoshino T,Saksela E

    更新日期:1992-10-21 00:00:00

  • Proliferative activity of plasma cells is the most relevant prognostic factor in elderly multiple myeloma patients.

    abstract::Although multiple myeloma (MM) is predominantly a disease of the elderly, few studies have focused on the identification of prognostic factors in this group of patients. Four hundred twenty five MM patients >65 years were uniformly treated with chemotherapy (MP or VCMP/VBAD). Multivariate analysis identified 4 factors...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20491

    authors: García-Sanz R,González-Fraile MI,Mateo G,Hernández JM,López-Berges MC,de las Heras N,Fernández-Calvo J,Ortega F,Portero JA,Bárez A,Galende J,Orfão A,San Miguel JF

    更新日期:2004-12-10 00:00:00

  • Seasonal variations do not affect the superiority of fecal immunochemical tests over guaiac tests for colorectal cancer screening.

    abstract::The aim of this study was to compare the seasonal variation in performance of a faecal immunochemical test for haemoglobin (FIT) and a guaiac test (gFOBT) for colorectal cancer screening. From June 2009 to May 2011, 18,290 screening participants (50-74 years old) performed OC-SENSOR quantitative FIT (1 sample) and Hem...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29187

    authors: Chausserie S,Levillain R,Puvinel J,Ferrand O,Ruiz A,Raginel T,Lantieri O,Launoy G,Guittet L

    更新日期:2015-04-15 00:00:00

  • The international classification of childhood cancer.

    abstract::The International Classification of Childhood Cancer (ICCC) updates the widely used Birch and Marsden classification scheme. ICCC is based on the second edition of the International Classification of Diseases for Oncology (ICD-O-2). The purpose of the new classification is to accommodate important changes in recogniti...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/(SICI)1097-0215(19961211)68:6<759::AID-IJC

    authors: Kramárová E,Stiller CA

    更新日期:1996-12-11 00:00:00

  • ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model.

    abstract::Angiogenesis inhibitors have been used to treat some cancers, but the therapeutic potential of these agents for gastric cancer has remained unclear. To investigate their therapeutic potential, we examined the effect of ZD6474, an agent that selectively targets vascular endothelial growth factor receptor-2 (VEGFR-2; KD...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21340

    authors: Arao T,Yanagihara K,Takigahira M,Takeda M,Koizumi F,Shiratori Y,Nishio K

    更新日期:2006-01-15 00:00:00

  • Smoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells.

    abstract::O6-alkylguanine-DNA alkyltransferase (MGMT) represents the first line of defense against the toxic, mutagenic and carcinogenic effects of O6-alkylguanine adducts in DNA. These adducts mediate the biological activity from a series of alkylating agents, such as the tobacco-specific nitrosamines, believed to contribute t...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21790

    authors: Povey AC,O'Donnell P,Barber P,Watson M,Margison GP,Santibáñez Koref MF

    更新日期:2006-07-15 00:00:00

  • Pigmentary characteristics, sun sensitivity and non-Hodgkin lymphoma.

    abstract::We report on pigmentary characteristics, sun sensitivity and some other possible risk factors for non-Hodgkin lymphoma (NHL) in people 20-74 years of age. A statewide case-control study was conducted in New South Wales, Australia, with population-based sampling of cases (n = 704) and controls (n = 694). Risk of NHL wa...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20128

    authors: Hughes AM,Armstrong BK,Vajdic CM,Turner J,Grulich A,Fritschi L,Milliken S,Kaldor J,Benke G,Kricker A

    更新日期:2004-06-20 00:00:00

  • Type of alcoholic beverage and cancer of the oral cavity, pharynx and oesophagus in an Italian area with high wine consumption.

    abstract::The role of different types of alcoholic beverage on cancer of the upper digestive tract was investigated in a case-control study conducted in the northern part of Italy on 305 male cases of cancer of the oral cavity and pharynx, 288 of oesophageal cancer and 1621 controls admitted to hospital for acute, non-neoplasti...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910460612

    authors: Barra S,Franceschi S,Negri E,Talamini R,La Vecchia C

    更新日期:1990-12-15 00:00:00

  • Expression of membrane type 1 matrix metalloproteinase (MT1-MMP) in A2058 melanoma cells is associated with MMP-2 activation and increased tumor growth and vascularization.

    abstract::Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase overexpressed in tumors, which plays a major role in the first step of pro-MMP-2 activation, leading to the generation of an intermediate 62 kDa species. The second step of MMP-2 activation that yields to the mature form is less understoo...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10134

    authors: Sounni NE,Baramova EN,Munaut C,Maquoi E,Frankenne F,Foidart JM,Noël A

    更新日期:2002-03-01 00:00:00

  • Dysregulated expression of transforming growth factor beta and its type-I and type-II receptors in basal-cell carcinoma.

    abstract::In mammals, transforming growth factor-beta (TGF-beta) is found in 3 highly homologous isoforms that exert their effects via heteromeric complexes of type-I and type-II receptors (TbetaR-I and TbetaR-II). TGF-beta regulates the growth and metabolism of various cell types, including keratinocytes. We have investigated ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19970516)71:4<505::aid-ijc

    authors: Furue M,Kato M,Nakamura K,Nashiro K,Kikuchi K,Okochi H,Miyazono K,Tamaki K

    更新日期:1997-05-16 00:00:00

  • Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase.

    abstract::Recently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable. The efficacy of its antitumor activity largely depends on the level of intracellular ASS, whi...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22322

    authors: Yoon CY,Shim YJ,Kim EH,Lee JH,Won NH,Kim JH,Park IS,Yoon DK,Min BH

    更新日期:2007-02-15 00:00:00

  • Heterotransplantation of small-cell carcinoma of the lung into nude mice: comparison of intracranial and subcutaneous routes.

    abstract::We compared and contrasted intracranial (i.c.) and subcutaneous (s.c.) heterotransplantation of small-cell carcinoma of the lung (SCCL) into athymic nude mice. Fresh human SCCL tumor specimens, tumor colonies grown in soft agarose and continuous cell lines were used. Tumors induced by the three types of specimens were...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910280617

    authors: Gazdar AF,Carney DN,Sims HL,Simmons A

    更新日期:1981-12-01 00:00:00

  • Glycoprotein 90K/MAC-2BP interacts with galectin-1 and mediates galectin-1-induced cell aggregation.

    abstract::The glycoprotein 90K was originally described as a tumor-secreted antigen and subsequently found to have immunostimulatory activity as well as other possible functions. This protein interacts with an endogenous lectin, galectin-3, and may play a role in tumor metastasis through this interaction. Because 90K is heavily...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1022>3

    authors: Tinari N,Kuwabara I,Huflejt ME,Shen PF,Iacobelli S,Liu FT

    更新日期:2001-01-15 00:00:00

  • Increased monocyte-mediated cytostasis of lymphoid cell lines in breast and lung cancer patients.

    abstract::Peripheral blood mononuclear cells of most normal adults and patients with breast or lung cancer were found to inhibit [3H] thymidine uptake by lymphoid cell lines in a growth inhibition assay. At effector:target cell ratios between 5:1 and 20:1, lung cancer patients and breast cancer patients, when compared to normal...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910230606

    authors: Jerrells TR,Dean JH,Richardson G,Cannon GB,Herberman RB

    更新日期:1979-06-15 00:00:00

  • Expression, subcellular localization and putative function of platelet-type 12-lipoxygenase in human prostate cancer cell lines of different metastatic potential.

    abstract::The involvement of 12-lipoxygenase (12-LOX) expression and function in tumor metastasis has been demonstrated in several murine tumor cell lines. In addition, 12-LOX expression was detected in human prostatic tumors and correlated to the clinical stage of disease. Here we provide data that human prostate cancer cell l...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(20000701)87:1<37::aid-ijc6>3.0.c

    authors: Timár J,Rásó E,Döme B,Li L,Grignon D,Nie D,Honn KV,Hagmann W

    更新日期:2000-07-01 00:00:00

  • Spontaneous and induced primary oncogenesis in natural killer (NK)-cell-deficient beige mutant mice.

    abstract::Spontaneous tumor development and primary oncogenesis were compared in a large number of NK4-deficient, homozygous C57Bl/6-bg/bg mice and their NK normal, heterozygous +/bg littermate controls. In a group of 167 retired breeders followed for spontaneous tumors, the probability of survival for mice eventually dying wit...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910350414

    authors: Haliotis T,Ball JK,Dexter D,Roder JC

    更新日期:1985-04-15 00:00:00

  • Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells.

    abstract::Cervical carcinogenesis is a consequence of persistent infection with high-risk human papillomaviruses (HPVs). Recent studies indicate that HPV-transformed cells actively instruct their microenvironment to promote carcinogenesis. Here, we demonstrate that cervical cancer cells activate monocytes to produce their own C...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.28549

    authors: Pahne-Zeppenfeld J,Schröer N,Walch-Rückheim B,Oldak M,Gorter A,Hegde S,Smola S

    更新日期:2014-05-01 00:00:00