| Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. | |
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MedLine Citation:
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PMID: 16740709 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hodgkin lymphoma (HL) is characterized by the presence of a small number of tumor cells in a rich background of inflammatory cells, but the contribution of the abundant nontumor cells to HL pathogenesis is poorly understood. We showed that migratory CD4(+) cells induced by HL cells were hyporesponsive to T-cell receptor stimulation and suppressed the activation/proliferation of the effector CD4(+) T cells in an autologous setting. We further showed that HL cells in the affected lymph nodes were surrounded by a large number of lymphocytes expressing both CC chemokine receptor 4 (CCR4) and FOXP3. These findings indicate that the migratory cells induced by HL cells function as regulatory T (Treg) cells so that these cells create a favorable environment for the tumor cells to escape from host immune system. In addition, we showed that a chimeric anti-CCR4 monoclonal antibody (mAb) could deplete CCR4(+) T cells and inhibit the migration of CD4(+)CD25(+) T cells in vitro. Recognition of the importance of CCR4(+) Treg cells in the pathogenesis of HL will allow rational design of more effective treatments, such as use of an anti-CCR4 mAb, to overcome the suppressive effect of CCR4(+) Treg cells on the host immune response to tumor cells. |
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Authors:
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Takashi Ishida; Toshihiko Ishii; Atsushi Inagaki; Hiroki Yano; Hirokazu Komatsu; Shinsuke Iida; Hiroshi Inagaki; Ryuzo Ueda |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer research Volume: 66 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-06-02 Completed Date: 2006-07-27 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 5716-22 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine and Molecular Science and Clinical Pathology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan. itakashi@med.nagoya-cu.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antibodies, Monoclonal / immunology, pharmacology Cell Line, Tumor Cell Movement / immunology Chemokine CCL17 Chemokines / biosynthesis, immunology Chemokines, CC / biosynthesis, immunology Flow Cytometry Forkhead Transcription Factors / biosynthesis, immunology Hodgkin Disease / immunology* Humans Lymphocyte Activation Lymphoma, Large B-Cell, Diffuse / immunology Receptors, CCR4 Receptors, Chemokine / biosynthesis, immunology* Receptors, Interleukin-2 / immunology T-Lymphocytes, Regulatory / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/CCL17 protein, human; 0/CCR4 protein, human; 0/Chemokine CCL17; 0/Chemokines; 0/Chemokines, CC; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Receptors, CCR4; 0/Receptors, Chemokine; 0/Receptors, Interleukin-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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