| Interferons induce CXCR3-cognate chemokine production by human metastatic melanoma. | |
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MedLine Citation:
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PMID: 20948440 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Immune-mediated cancer regression requires tumor infiltration by antigen-specific effector T cells, but lymphocytes are commonly sparse in melanoma metastases. Activated T cells express CXCR3, whose cognate chemokines are CXCL9/MIG, CXCL10/IP-10, and CXCL11/I-TAC. Little is known about expression of these chemokines in lymph node (LN) metastases of melanoma. We evaluated whether metastatic melanoma induces these CXCR3-cognate chemokines in human LN-derived tissues. In addition, as these chemokines can be induced by interferon (IFN), we evaluated whether type I or II IFNs (IFN-α or IFN-γ, respectively) can modulate chemokine expression in an in vitro model of the human tumor microenvironment. Production of CXCL9-11 by melanoma-infiltrated nodes (MIN) was no different than tumor-free nodes; both produced less chemokine than activated LN (sentinel immunized nodes, SIN). These data suggest that melanoma infiltration into LN neither induces nor reduces CXCL9-11. Stimulation with IFN-α or IFN-γ increased production of CXCL10-11 from MIN, but not tumor-free node or SIN. IFN-γ also increased production of CXCL9 in MIN. In IFN-treated SIN, CD14+ cells were the primary source of CXCL9-11, whereas melanoma cells were the source of chemokine in MIN. Melanoma cells in MIN express IFN receptors. Consistent with these observations, multiple human melanoma lines expressed IFN receptors and produced CXCL9-11 in response to IFN treatment. Thus, melanoma infiltration of LN is insufficient to induce the production of CXCL9-11, but melanoma may be a significant source of IFN-induced chemokines. Collectively, these data suggest that IFN-α or IFN-γ may act in the tumor microenvironment to increase the chemotactic gradient for CXCR3+ T cells. |
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Authors:
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Lynn T Dengel; Allison G Norrod; Briana L Gregory; Eleanor Clancy-Thompson; Marie D Burdick; Robert M Strieter; Craig L Slingluff; David W Mullins |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunotherapy (Hagerstown, Md. : 1997) Volume: 33 ISSN: 1537-4513 ISO Abbreviation: J. Immunother. Publication Date: 2010 Nov-Dec |
Date Detail:
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Created Date: 2010-10-26 Completed Date: 2011-05-24 Revised Date: 2012-02-14 |
Medline Journal Info:
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Nlm Unique ID: 9706083 Medline TA: J Immunother Country: United States |
Other Details:
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Languages: eng Pagination: 965-74 Citation Subset: IM |
Affiliation:
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Human Immune Therapy Center, University of Virginia School of Medicine, Charlottesville, VA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Chemokine CXCL10 / genetics, immunology, metabolism* Chemokine CXCL11 / genetics, metabolism* Chemokine CXCL9 / genetics, immunology, metabolism* Humans Interferon Type I / immunology, metabolism Interferon-gamma / immunology, metabolism Lymph Nodes / immunology, metabolism*, pathology Lymphatic Metastasis Lymphocyte Activation Melanoma Receptors, CXCR3 / immunology, metabolism* Skin Neoplasms T-Lymphocytes Tumor Microenvironment |
| Grant Support | |
ID/Acronym/Agency:
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P30 CA044579/CA/NCI NIH HHS; P30 CA044579-19/CA/NCI NIH HHS; R01 CA057653-17/CA/NCI NIH HHS; R01 CA057653-18/CA/NCI NIH HHS; R01 CA134799/CA/NCI NIH HHS; R01 CA134799-02/CA/NCI NIH HHS; R01 CA57653/CA/NCI NIH HHS; T32 HL007849/HL/NHLBI NIH HHS; T32 HL007849-07/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CXCR3 protein, human; 0/Chemokine CXCL10; 0/Chemokine CXCL11; 0/Chemokine CXCL9; 0/Interferon Type I; 0/Receptors, CXCR3; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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