Source:http://linkedlifedata.com/resource/pubmed/id/18503261
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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
2008-5-27
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pubmed:abstractText |
The cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule on T cells acts to maintain homeostasis by regulating the proliferation of recently activated T cells. Blockade of CTLA-4 by anti-CTLA-4 antibody enhances T cell responses and has elicited significant tumor regression in some cancer patients. Clinical trials are ongoing to investigate the efficacy of anti-CTLA-4 antibody as a cancer therapeutic. Reports from several clinical trials have documented the occurrence of adverse events in patients treated with anti-CTLA-4 antibody which have some similarities with autoimmune conditions and have been termed immune-related adverse events (irAEs). Most irAEs are reversible with corticosteroid therapy. Some investigators suggest that irAEs occur in the same patients who have anti-tumor responses as a result of the anti-CTLA-4 antibody. Immunologic mechanisms to explain why irAEs occur in some patients have not been reported. Here we report that bladder cancer patients treated with anti-CTLA-4 antibody have increased levels of the Th1 cytokine IFN-gamma detected in plasma samples. Although IFN-gamma is a potent anti-tumor and inflammatory cytokine, increased levels of IFN-gamma were not associated with irAEs in our patients. However, in one patient who experienced an irAE consisting of ischemic papillopathy and optic neuritis, we documented high pre-therapy levels of the Th2 cytokine IL-10 which decreased after treatment with anti-CTLA-4 antibody. The decrease in plasma IL-10 concentration coincided with the patient's irAE. We propose that decreased levels of IL-10 after treatment with anti-CTLA-4 therapy may be responsible for irAEs in some patients and needs to be further investigated in larger studies.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10
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pubmed:status |
MEDLINE
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pubmed:issn |
1424-9634
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18503261-Aged,
pubmed-meshheading:18503261-Antibodies, Monoclonal,
pubmed-meshheading:18503261-Antigens, CD,
pubmed-meshheading:18503261-Antigens, Differentiation,
pubmed-meshheading:18503261-CTLA-4 Antigen,
pubmed-meshheading:18503261-Clinical Trials as Topic,
pubmed-meshheading:18503261-Humans,
pubmed-meshheading:18503261-Interferon-gamma,
pubmed-meshheading:18503261-Interleukin-10,
pubmed-meshheading:18503261-Male,
pubmed-meshheading:18503261-Urinary Bladder Neoplasms
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pubmed:year |
2008
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pubmed:articleTitle |
Concurrent decrease in IL-10 with development of immune-related adverse events in a patient treated with anti-CTLA-4 therapy.
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pubmed:affiliation |
Department of Genitourinary Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.
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pubmed:publicationType |
Journal Article,
Case Reports
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