Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2010

Open Access 01-12-2010 | Research

miR-17-92 expression in differentiated T cells - implications for cancer immunotherapy

Authors: Kotaro Sasaki, Gary Kohanbash, Aki Hoji, Ryo Ueda, Heather A McDonald, Todd A Reinhart, Jeremy Martinson, Michael T Lotze, Francesco M Marincola, Ena Wang, Mitsugu Fujita, Hideho Okada

Published in: Journal of Translational Medicine | Issue 1/2010

Login to get access

Abstract

Background

Type-1 T cells are critical for effective anti-tumor immune responses. The recently discovered microRNAs (miRs) are a large family of small regulatory RNAs that control diverse aspects of cell function, including immune regulation. We identified miRs differentially regulated between type-1 and type-2 T cells, and determined how the expression of such miRs is regulated.

Methods

We performed miR microarray analyses on in vitro differentiated murine T helper type-1 (Th1) and T helper type-2 (Th2) cells to identify differentially expressed miRs. We used quantitative RT-PCR to confirm the differential expression levels. We also used WST-1, ELISA, and flow cytometry to evaluate the survival, function and phenotype of cells, respectively. We employed mice transgenic for the identified miRs to determine the biological impact of miR-17-92 expression in T cells.

Results

Our initial miR microarray analyses revealed that the miR-17-92 cluster is one of the most significantly over-expressed miR in murine Th1 cells when compared with Th2 cells. RT-PCR confirmed that the miR-17-92 cluster expression was consistently higher in Th1 cells than Th2 cells. Disruption of the IL-4 signaling through either IL-4 neutralizing antibody or knockout of signal transducer and activator of transcription (STAT)6 reversed the miR-17-92 cluster suppression in Th2 cells. Furthermore, T cells from tumor bearing mice and glioma patients had decreased levels of miR-17-92 when compared with cells from non-tumor bearing counterparts. CD4+ T cells derived from miR-17-92 transgenic mice demonstrated superior type-1 phenotype with increased IFN-γ production and very late antigen (VLA)-4 expression when compared with counterparts derived from wild type mice. Human Jurkat T cells ectopically expressing increased levels of miR-17-92 cluster members demonstrated increased IL-2 production and resistance to activation-induced cell death (AICD).

Conclusion

The type-2-skewing tumor microenvironment induces the down-regulation of miR-17-92 expression in T cells, thereby diminishing the persistence of tumor-specific T cells and tumor control. Genetic engineering of T cells to express miR-17-92 may represent a promising approach for cancer immunotherapy.
Appendix
Available only for authorised users
Literature
1.
Nishimura F, Dusak JE, Eguchi J, Zhu X, Gambotto A, Storkus WJ, Okada H: Adoptive transfer of Type 1 CTL mediates effective anti-central nervous system tumor response: critical roles of IFN-inducible protein-10. Cancer Res. 2006, 66: 4478-4487. 10.1158/0008-5472.CAN-05-3825.PubMedCrossRef
2.
Fujita M, Zhu X, Sasaki K, Ueda R, Low KL, Pollack IF, Okada H: Inhibition of STAT3 promotes the efficacy of adoptive transfer therapy using type-1 CTLs by modulation of the immunological microenvironment in a murine intracranial glioma. J Immunol. 2008, 180: 2089-2098.PubMedCrossRef
3.
Fujita M, Zhu X, Ueda R, Sasaki K, Kohanbash G, Kastenhuber ER, McDonald HA, Gibson GA, Watkins SC, Muthuswamy R: Effective Immunotherapy against Murine Gliomas Using Type 1 Polarizing Dendritic Cells--Significant Roles of CXCL10. Cancer Res. 2009, 69: 1587-1595. 10.1158/0008-5472.CAN-08-2915.PubMedCrossRef
4.
Sasaki K, Zhao X, Pardee AD, Ueda R, Fujita M, Sehra S, Kaplan MH, Kane LP, Okada H, Storkus WJ: Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivo. The Journal of Immunology. 2008, 181: 104-108.PubMedPubMedCentralCrossRef
5.
Sasaki K, Pardee AD, Okada H, Storkus WJ: IL-4 inhibits VLA-4 expression on Tc1 cells resulting in poor tumor infiltration and reduced therapy benefit. Eur J Immunol. 2008, 38: 2865-2873. 10.1002/eji.200838334.PubMedPubMedCentralCrossRef
6.
Zhu X, Nishimura F, Sasaki K, Fujita M, Dusak JE, Eguchi J, Fellows-Mayle W, Storkus WJ, Walker PR, Salazar AM, Okada H: Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models. J Transl Med. 2007, 5: 10-10.1186/1479-5876-5-10.PubMedPubMedCentralCrossRef
7.
Sasaki K, Zhu X, Vasquez C, Nishimura F, Dusak JE, Huang J, Fujita M, Wesa A, Potter DM, Walker PR: Preferential expression of very late antigen-4 on type 1 CTL cells plays a critical role in trafficking into central nervous system tumors. Cancer Res. 2007, 67: 6451-6458. 10.1158/0008-5472.CAN-06-3280.PubMedCrossRef
8.
Roussel E, Gingras MC, Grimm EA, Bruner JM, Moser RP: Predominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas. Clin Exp Immunol. 1996, 105: 344-352. 10.1046/j.1365-2249.1996.d01-753.x.PubMedPubMedCentralCrossRef
9.
Weller M, Fontana A: The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-beta, T-cell apoptosis, and the immune privilege of the brain. Brain Res. 1995, 21: 128-151. 10.1016/0165-0173(95)00010-0.CrossRef
10.
Nitta T, Hishii M, Sato K, Okumura K: Selective expression of interleukin-10 gene within glioblastoma multiforme. Brain Res. 1994, 649: 122-128. 10.1016/0006-8993(94)91055-3.PubMedCrossRef
11.
Jarnicki AG, Lysaght J, Todryk S, Mills KHG: Suppression of Antitumor Immunity by IL-10 and TGF-beta-Producing T Cells Infiltrating the Growing Tumor: Influence of Tumor Environment on the Induction of CD4+ and CD8+ Regulatory T Cells. J Immunol. 2006, 177: 896-904.PubMedCrossRef
12.
Prokopchuk O, Liu Y, Henne-Bruns D, Kornmann M: Interleukin-4 enhances proliferation of human pancreatic cancer cells: evidence for autocrine and paracrine actions. Br J Cancer. 2005, 92: 921-928. 10.1038/sj.bjc.6602416.PubMedPubMedCentralCrossRef
13.
Seo N, Hayakawa S, Takigawa M, Tokura Y: Interleukin-10 expressed at early tumour sites induces subsequent generation of CD4+ T-regulatory cells and systemic collapse of antitumour immunity. Immunology. 2001, 103: 449-457. 10.1046/j.1365-2567.2001.01279.x.PubMedPubMedCentralCrossRef
14.
Hammond SM: RNAi, microRNAs, and human disease. Cancer Chemother Pharmacol. 2006, 58 (Suppl 1): s63-68. 10.1007/s00280-006-0318-2.PubMedCrossRef
15.
Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, Lindholm M, Hedtjarn M, Hansen HF, Berger U: LNA-mediated microRNA silencing in non-human primates. Nature. 2008, 452: 896-899. 10.1038/nature06783.PubMedCrossRef
16.
Cheng AM, Byrom MW, Shelton J, Ford LP: Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 2005, 33: 1290-1297. 10.1093/nar/gki200.PubMedPubMedCentralCrossRef
17.
Xu P, Guo M, Hay BA: MicroRNAs and the regulation of cell death. Trends Genet. 2004, 20: 617-624. 10.1016/j.tig.2004.09.010.PubMedCrossRef
18.
Karp X, Ambros V: Developmental biology. Encountering microRNAs in cell fate signaling. Science. 2005, 310: 1288-1289. 10.1126/science.1121566.PubMedCrossRef
19.
Chen CZ, Li L, Lodish HF, Bartel DP: MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004, 303: 83-86. 10.1126/science.1091903.PubMedCrossRef
20.
Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M: A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004, 432: 226-230. 10.1038/nature03076.PubMedCrossRef
21.
Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL: Regulation of the germinal center response by microRNA-155. Science. 2007, 316: 604-608. 10.1126/science.1141229.PubMedCrossRef
22.
O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D: MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA. 2007, 104: 1604-1609. 10.1073/pnas.0610731104.PubMedPubMedCentralCrossRef
23.
Ueda R, Kohanbash G, Sasaki K, Fujita M, Zhu X, Kastenhuber ER, McDonald HA, Potter DM, Hamilton RL, Lotze MT: Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc Natl Acad Sci USA. 2009, 106: 10746-10751. 10.1073/pnas.0811817106.PubMedPubMedCentralCrossRef
24.
Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K: Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008, 9: 405-414. 10.1038/ni1575.PubMedPubMedCentralCrossRef
25.
Xiao C, Rajewsky K: MicroRNA control in the immune system: basic principles. Cell. 2009, 136: 26-36. 10.1016/j.cell.2008.12.027.PubMedCrossRef
26.
Tanzer A, Stadler PF: Molecular Evolution of a MicroRNA Cluster. Journal of Molecular Biology. 2004, 339: 327-335. 10.1016/j.jmb.2004.03.065.PubMedCrossRef
27.
He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM: A microRNA polycistron as a potential human oncogene. Nature. 2005, 435: 828-833. 10.1038/nature03552.PubMedPubMedCentralCrossRef
28.
Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T: A Polycistronic MicroRNA Cluster, miR-17-92, Is Overexpressed in Human Lung Cancers and Enhances Cell Proliferation. Cancer Res. 2005, 65: 9628-9632. 10.1158/0008-5472.CAN-05-2352.PubMedCrossRef
29.
Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, Yamada H, Suzuki M, Nagino M, Nimura Y: Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 2007, 26: 6099-6105. 10.1038/sj.onc.1210425.PubMedCrossRef
30.
Lawrie CH: MicroRNA expression in lymphoma. Expert Opin Biol Ther. 2007, 7: 1363-1374. 10.1517/14712598.7.9.1363.PubMedCrossRef
31.
Rinaldi A, Poretti G, Kwee I, Zucca E, Catapano CV, Tibiletti MG, Bertoni F: Concomitant MYC and microRNA cluster miR-17-92 (C13orf25) amplification in human mantle cell lymphoma. Leuk Lymphoma. 2007, 48: 410-412. 10.1080/10428190601059738.PubMedCrossRef
32.
Ren J, Jin P, Wang E, Marincola F, Stroncek D: MicroRNA and gene expression patterns in the differentiation of human embryonic stem cells. Journal of Translational Medicine. 2009, 7: 20-10.1186/1479-5876-7-20.PubMedPubMedCentralCrossRef
33.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.PubMedCrossRef
34.
35.
Eguchi J, Hiroishi K, Ishii S, Baba T, Matsumura T, Hiraide A, Okada H, Imawari M: Interleukin-4 gene transduced tumor cells promote a potent tumor-specific Th1-type response in cooperation with interferon-alpha transduction. Gene Ther. 2005, 12: 733-741. 10.1038/sj.gt.3302401.PubMedCrossRef
36.
Kennedy R, Celis E: Multiple roles for CD4+ T cells in anti-tumor immune responses. Immunological Reviews. 2008, 222: 129-144. 10.1111/j.1600-065X.2008.00616.x.PubMedCrossRef
37.
Brenner D, Krammer PH, Arnold Ri: Concepts of activated T cell death. Critical Reviews in Oncology/Hematology. 2008, 66: 52-64. 10.1016/j.critrevonc.2008.01.002.PubMedCrossRef
38.
Jiang T, Han Z, Chen S, Wu C, Tang Y, Qian C, Chen Y, Zhou Y, Zhu Y, Gu M: Resistance to activation-induced cell death and elevated FLIP(L) expression of CD4+ T cells in a polyI:C-induced primary biliary cirrhosis mouse model. Clin Exp Med. 2009
39.
Woods K, Thomson JM, Hammond SM: Direct Regulation of an Oncogenic Micro-RNA Cluster by E2F Transcription Factors. J Biol Chem. 2007, 282: 2130-2134. 10.1074/jbc.C600252200.PubMedCrossRef
40.
Sylvestre Y, De Guire V, Querido E, Mukhopadhyay UK, Bourdeau V, Major F, Ferbeyre G, Chartrand P: An E2F/miR-20a Autoregulatory Feedback Loop. J Biol Chem. 2007, 282: 2135-2143. 10.1074/jbc.M608939200.PubMedCrossRef
41.
O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT: c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005, 435: 839-843. 10.1038/nature03677.PubMedCrossRef
42.
Brock M, Trenkmann M, Gay RE, Michel BA, Gay S, Fischler M, Ulrich S, Speich R, Huber LC: Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ Res. 2009, 104: 1184-1191. 10.1161/CIRCRESAHA.109.197491.PubMedCrossRef
43.
Northcott PA, Fernandez LA, Hagan JP, Ellison DW, Grajkowska W, Gillespie Y, Grundy R, Van Meter T, Rutka JT, Croce CM: The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors. Cancer Res. 2009, 69: 3249-3255. 10.1158/0008-5472.CAN-08-4710.PubMedPubMedCentralCrossRef
44.
Uziel T, Karginov FV, Xie S, Parker JS, Wang YD, Gajjar A, He L, Ellison D, Gilbertson RJ, Hannon G, Roussel MF: The miR-17~92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci USA. 2009, 106: 2812-2817. 10.1073/pnas.0809579106.PubMedPubMedCentralCrossRef
45.
Sasaki K, Pardee AD, Qu Y, Zhao X, Ueda R, Kohanbash G, Bailey LM, Okada H, Muthuswamy R, Kalinski P: IL-4 Suppresses Very Late Antigen-4 Expression Which is Required for Therapeutic Th1 T-cell Trafficking Into Tumors. Journal of Immunotherapy. 2009, 32: 793-802. 10.1097/CJI.0b013e3181acec1e.PubMedPubMedCentralCrossRef
46.
Ehi K, Ishigami S, Masamoto I, Uenosono Y, Natsugoe S, Arigami T, Arima H, Kijima Y, Yoshinaka H, Yanagita S: Analysis of T-helper type 1 and 2 cells and T-cytotoxic type 1 and 2 cells of sentinel lymph nodes in breast cancer. Oncol Rep. 2008, 19: 601-607.PubMed
47.
Tatsumi T, Herrem CJ, Olson WC, Finke JH, Bukowski RM, Kinch MS, Ranieri E, Storkus WJ: Disease stage variation in CD4+ and CD8+ T-cell reactivity to the receptor tyrosine kinase EphA2 in patients with renal cell carcinoma. Cancer Res. 2003, 63: 4481-4489.PubMed
48.
Inomata M, Tagawa H, Guo YM, Kameoka Y, Takahashi N, Sawada K: MicroRNA-17-92 down-regulates expression of distinct targets in different B-cell lymphoma subtypes. Blood. 2009, 113: 396-402. 10.1182/blood-2008-07-163907.PubMedCrossRef
49.
Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A: Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet. 2006, 38: 1060-1065. 10.1038/ng1855.PubMedPubMedCentralCrossRef
50.
Volinia S, Calin GA, Liu C-G, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006, 103: 2257-2261. 10.1073/pnas.0510565103.PubMedPubMedCentralCrossRef
51.
Taguchi A, Yanagisawa K, Tanaka M, Cao K, Matsuyama Y, Goto H, Takahashi T: Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Cancer Res. 2008, 68: 5540-5545. 10.1158/0008-5472.CAN-07-6460.PubMedCrossRef
52.
Sitkovsky M, Lukashev D: Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors. Nat Rev Immunol. 2005, 5: 712-721. 10.1038/nri1685.PubMedCrossRef
53.
Semenza GL: Hypoxia-inducible factor 1: master regulator of O2 homeostasis. Current Opinion in Genetics & Development. 1998, 8: 588-594. 10.1016/S0959-437X(98)80016-6.CrossRef
54.
Cramer T, Yamanishi Y, Clausen BE, Förster I, Pawlinski R, Mackman N, Haase VH, Jaenisch R, Corr M, Nizet V: HIF-1α Is Essential for Myeloid Cell-Mediated Inflammation. 2003, 112: 645-657.
55.
Brand K, Hermfisse U: Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species. FASEB J. 1997, 11: 388-395.PubMed
56.
Neumann AK, Yang J, Biju MP, Joseph SK, Johnson RS, Haase VH, Freedman BD, Turka LA: Hypoxia inducible factor 1α regulates T cell receptor signal transduction. Proceedings of the National Academy of Sciences of the United States of America. 2005, 102: 17071-17076. 10.1073/pnas.0506070102.PubMedPubMedCentralCrossRef
57.
Eltzschig HK, Thompson LF, Karhausen J, Cotta RJ, Ibla JC, Robson SC, Colgan SP: Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood. 2004, 104: 3986-3992. 10.1182/blood-2004-06-2066.PubMedCrossRef
58.
Kojima H, Gu H, Nomura S, Caldwell CC, Kobata T, Carmeliet P, Semenza GL, Sitkovsky MV: Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1α-deficient chimeric mice. Proceedings of the National Academy of Sciences of the United States of America. 2002, 99: 2170-2174. 10.1073/pnas.052706699.PubMedPubMedCentralCrossRef
59.
Lukashev D, Klebanov B, Kojima H, Grinberg A, Ohta A, Berenfeld L, Wenger RH, Ohta A, Sitkovsky M: Cutting Edge: Hypoxia-Inducible Factor 1{alpha} and Its Activation-Inducible Short Isoform I.1 Negatively Regulate Functions of CD4+ and CD8+ T Lymphocytes. J Immunol. 2006, 177: 4962-4965.PubMedCrossRef
60.
Guo J, Lu W, Shimoda LA, Semenza GL, Georas SN: Enhanced interferon-gamma gene expression in T Cells and reduced ovalbumin-dependent lung eosinophilia in hypoxia-inducible factor-1-alpha-deficient mice. Int Arch Allergy Immunol. 2009, 149: 98-102. 10.1159/000189191.PubMedPubMedCentralCrossRef
61.
Thiel M, Caldwell CC, Kreth S, Kuboki S, Chen P, Smith P, Ohta A, Lentsch AB, Lukashev D, Sitkovsky MV: Targeted deletion of HIF-1alpha gene in T cells prevents their inhibition in hypoxic inflamed tissues and improves septic mice survival. PLoS One. 2007, 2: e853-10.1371/journal.pone.0000853.PubMedPubMedCentralCrossRef
62.
Nagai S, Hashimoto S, Yamashita T, Toyoda N, Satoh T, Suzuki T, Matsushima K: Comprehensive gene expression profile of human activated T(h)1- and T(h)2-polarized cells. Int Immunol. 2001, 13: 367-376. 10.1093/intimm/13.3.367.PubMedCrossRef
63.
Abraham RT, Weiss A: Jurkat T cells and development of the T-cell receptor signalling paradigm. Nat Rev Immunol. 2004, 4: 301-308. 10.1038/nri1330.PubMedCrossRef
64.
Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR: Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008, 132: 875-886. 10.1016/j.cell.2008.02.019.PubMedPubMedCentralCrossRef
65.
Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP: Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes. Science. 2006
66.
Pule MA, Savoldo B, Myers GD, Rossig C, Russell HV, Dotti G, Huls MH, Liu E, Gee AP, Mei Z: Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008, 14: 1264-1270. 10.1038/nm.1882.PubMedPubMedCentralCrossRef
Metadata
Title
miR-17-92 expression in differentiated T cells - implications for cancer immunotherapy
Authors
Kotaro Sasaki
Gary Kohanbash
Aki Hoji
Ryo Ueda
Heather A McDonald
Todd A Reinhart
Jeremy Martinson
Michael T Lotze
Francesco M Marincola
Ena Wang
Mitsugu Fujita
Hideho Okada
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2010
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-8-17

Other articles of this Issue 1/2010

Journal of Translational Medicine 1/2010 Go to the issue

Research

Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits

Research

Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A*2402

Research

Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients

Research

S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis)

Editorial

Cell and gene therapies: moving from research to clinic

Research

Prognostic impact of ZAP-70 expression in chronic lymphocytic leukemia: mean fluorescence intensity T/B ratio versus percentage of positive cells
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits