Histamine: A novel approach to cancer immunotherapy

被引:40
作者
Hellstrand, K
Brune, M
Naredi, P
Mellqvist, UH
Hansson, M
Gehlsen, KR
Hermodsson, S
机构
[1] Gothenburg Univ, Dept Virol, S-41346 Gothenburg, Sweden
[2] Gothenburg Univ, Dept Hematol, S-41346 Gothenburg, Sweden
[3] Gothenburg Univ, Dept Surg, S-41346 Gothenburg, Sweden
[4] Maxim Pharmaceut, San Diego, CA USA
关键词
D O I
10.3109/07357900009012178
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The functions of intratumoral lymphocytes in many human malignant tumors are inhibited by reactive oxygen species (ROS), generated by adjacent monocytes/macrophages (MO). In vitro data suggest that immunotherapeutic cytokines such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha) only weakly activate T cells or natural killer (NK) cells in a reconstituted environment of oxidative stress and that inhibitors of the formation of ROS or scavengers of ROS synergize with IL-2 and IFN-alpha to activate T cells and NK cells. In this review, we focus on the immunoenhancing properties of histamine, a biogenic amine. Histamine inhibits ROS formation in MO via H2-receptors; thereby, histamine protects NK cells from MO-mediated inhibition and synergizes with IL-2 and IFN-alpha to induce killing of NK cell-sensitive human tumor cells in vitro. Histamine also optimizes cytokine-induced activation of several subsets of T cells by affording protection against MO-inflicted oxidative inhibition. The putative clinical benefit of histamine as an adjunct to immunotherapy with IL-2 and/or IFN-alpha is currently evaluated in clinical trials in metastatic malignant melanoma and acute myelogenous leukemia.
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收藏
页码:347 / 355
页数:9
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