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Addition of histami...
Addition of histamine to interleukin 2 treatment augments type 1 T-cell responses in patients with melanoma in vivo: immunologic results from a randomized clinical trial of interleukin 2 with or without histamine (MP 104)
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Asemissen, Anne Marie (författare)
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Scheibenbogen, Carmen (författare)
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Letsch, Anne (författare)
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visa fler...
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- Hellstrand, Kristoffer, 1956 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin, Avdelningen för klinisk virologi,Institute of Laboratory Medicine, Dept of Clinical Virology
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- Bergh Thorén, Fredrik, 1976 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin, Avdelningen för klinisk virologi,Institute of Laboratory Medicine, Dept of Clinical Virology
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Gehlsen, Kurt (författare)
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Schmittel, Alexander (författare)
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Thiel, Eckhard (författare)
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Keilholz, Ulrich (författare)
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visa färre...
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(creator_code:org_t)
- 2005
- 2005
- Engelska.
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Ingår i: Clin Cancer Res. - 1078-0432. ; 11:1, s. 290-7
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- PURPOSE: Preclinical investigations suggest that histamine dihydrochloride (HDC) protects T cells and natural killer cells from inhibition by monocyte-derived reactive oxygen metabolites and synergizes with interleukin (IL) 2 in inducing T-cell activation. Here, we investigate whether this mechanism is operational in patients with melanoma treated with HDC as an adjunct to IL-2. EXPERIMENTAL DESIGN: Melanoma patients having liver metastases were treated with IL-2 with or without HDC within a randomized, multicenter, phase III trial. The effect of HDC on type 1 and type 2 T-cell cytokine production was investigated in peripheral blood samples from 19 patients with the use of intracellular cytokine flow cytometry. Melanoma-specific T-cell responses were analyzed in eight HLA-A2-positive patients. RESULTS: Frequencies of CD3+ T cells producing IFN-gamma (type 1 T cells) in response to phorbol myristate acetate/ionomycin increased (median, 1.8-fold) in patients receiving IL-2 plus HDC but not in those receiving IL-2 alone (P < 0.01 for comparison between arms). In contrast, the number of IL-13-producing type 2 T cells that increased in patients after treatment with IL-2 was not modulated by HDC. Melanoma- and tyrosinase-specific IFN-gamma and IL-13-producing T cells were detected in two of four HLA-A2-positive patients with melanoma following treatment with HDC + IL-2. CONCLUSIONS: Treatment of patients with stage IV melanoma with HDC in combination with IL-2 increases type 1 T-cell responses and may promote induction of melanoma-specific T cells. These effects are of relevance for tumor immunotherapy and provide a potential mechanism for the clinical efficacy of HDC added to IL-2.
Nyckelord
- Antigens
- CD3/biosynthesis
- Cell Line
- Tumor
- Chromatography
- High Pressure Liquid
- Cytokines/biosynthesis
- Flow Cytometry
- Histamine/ therapeutic use
- Histocompatibility Testing
- Humans
- Interferon Type II/metabolism
- Interleukin-13/metabolism
- Interleukin-2/metabolism/ therapeutic use
- K562 Cells
- Leukocytes
- Mononuclear/metabolism
- Liver Neoplasms/ drug therapy/secondary
- Lymphocyte Activation
- Melanoma/ drug therapy/metabolism
- Monocytes/metabolism
- Neoplasm Metastasis
- Peptides/chemistry
- Reactive Oxygen Species
- T-Lymphocytes/immunology/ metabolism
- Time Factors
- Treatment Outcome
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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