| Hepatocellular carcinoma immunopathogenesis: clinical evidence for global T cell defects and an immunomodulatory role for soluble CD25 (sCD25). | |
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MedLine Citation:
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PMID: 19714465 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The mechanisms involved in hepatocellular carcinoma (HCC) establishing an immunologically tolerogenic tumor environment remain poorly characterized. AIMS: This study evaluates effector T cell responses and soluble IL-2 receptor alpha chains (sCD25) in relation to HCC stage/survival and characterizes the impact of sCD25 on effectors. METHODS: Effector cell responses with serum from HCC patients and in serum free conditions were assessed by IFN-gamma ELISpot, proliferation and ATP production assays at baseline, after depletion of sCD25, and after supplementation with recombinant sCD25. Sera sCD25 were measured by ELISA and any relationship with stage/survival was determined. RESULTS: Hepatocellular carcinoma patients had marked global impairment in T cell responses at baseline which correlate with tumor burden and poor outcome. The impairment in immune responses is characterized by low IFN-gamma production, cell proliferation, and ATP production. Effector responses are impaired by serum from HCC patients in a dose-dependent manner, implicating soluble factors in the observed immunosuppression. Significant elevations in serum levels of sCD25 are found in patients with HCC, which correlate with tumor burden and a worse survival. T cell reactivity is inversely proportional to serum level of sCD25. Impaired T cell responses improve with sCD25 depletion from HCC serum or IL-2 supplementation suggesting impairment in IL-2 signaling. In contrast, adding increasing doses of sCD25 suppresses effector T cells, which partly involves induction of apoptosis. CONCLUSIONS: These findings show that HCC patients have blunted T cell immunity that is partly related to elevated levels of sCD25, supporting a novel immuno-inhibitory role for this soluble receptor. |
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Authors:
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Roniel Cabrera; Miguel Ararat; Mengde Cao; Yiling Xu; Clive Wasserfall; Mark A Atkinson; Chen Liu; David R Nelson |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Digestive diseases and sciences Volume: 55 ISSN: 1573-2568 ISO Abbreviation: Dig. Dis. Sci. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-13 Completed Date: 2010-02-18 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 7902782 Medline TA: Dig Dis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 484-95 Citation Subset: AIM; IM |
Affiliation:
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Section of Hepatobiliary Diseases, Department of Medicine, University of Florida, 1600 SW Archer Rd, PO Box 100214, Gainesville, FL 32610-0214, USA. cabrer@medicine.ufl.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Carcinoma, Hepatocellular / blood, immunology*, pathology Cell Proliferation Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Humans Immunity, Cellular* Interleukin-2 Receptor alpha Subunit / blood, immunology* Liver Neoplasms / blood, immunology*, pathology Male Middle Aged T-Lymphocytes / immunology* Tumor Cells, Cultured Tumor Markers, Biological / blood, immunology |
| Grant Support | |
ID/Acronym/Agency:
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K24 CA139570-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/IL2RA protein, human; 0/Interleukin-2 Receptor alpha Subunit; 0/Tumor Markers, Biological |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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