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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2009-4-16
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pubmed:databankReference |
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pubmed:abstractText |
Preclinical animal models have largely ignored the immune-suppressive mechanisms that are important in human cancers. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in nonmalignant cells by cancer, we examined T-cell function in the chronic lymphocytic leukemia (CLL) Emu-TCL1 transgenic mouse model. With development of leukemia, Emu-TCL1 transgenic mice developed functional T-cell defects and alteration of gene and protein expression closely resembling changes seen in CLL human patients. Furthermore, infusion of CLL cells into young Emu-TCL1 mice induced defects comparable to those seen in mice with developed leukemia, demonstrating a causal relationship between leukemia and the T-cell defects. Altered pathways involved genes regulating actin remodeling, and T cells exhibited dysfunctional immunological synapse formation and T-cell signaling, which was reversed by the immunomodulatory drug lenalidomide. These results further demonstrate the utility of this animal model of CLL and define a versatile model to investigate both the molecular mechanisms of cancer-induced immune suppression and immunotherapeutic repair strategies.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-10068672,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-10835683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-11134512,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-11135576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-11224518,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-11606070,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-11731799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-11828322,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-11875039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-12011454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-12070023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-15711558,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-15914560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-15965501,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-16173164,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-16670263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-16864779,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-1696684,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-17088571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-17259969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-17638850,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-18334676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-18427150,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-18551193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19332800-7540654
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6250-5
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:19332800-Animals,
pubmed-meshheading:19332800-Disease Models, Animal,
pubmed-meshheading:19332800-Disease Progression,
pubmed-meshheading:19332800-Gene Expression Profiling,
pubmed-meshheading:19332800-Humans,
pubmed-meshheading:19332800-Immunological Synapses,
pubmed-meshheading:19332800-Immunotherapy,
pubmed-meshheading:19332800-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:19332800-Mice,
pubmed-meshheading:19332800-Mice, Transgenic,
pubmed-meshheading:19332800-Proto-Oncogene Proteins,
pubmed-meshheading:19332800-Signal Transduction,
pubmed-meshheading:19332800-T-Lymphocytes,
pubmed-meshheading:19332800-Thalidomide
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pubmed:year |
2009
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pubmed:articleTitle |
E(mu)-TCL1 mice represent a model for immunotherapeutic reversal of chronic lymphocytic leukemia-induced T-cell dysfunction.
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pubmed:affiliation |
Department of Medical Oncology, The Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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