Histamine in cancer immunotherapy: a preclinical background.
Natural killer (NK) cells and T cells are the primary targets of interleukin-2 (IL-2) and other cytokines used in cancer immunotherapy. However, these tumoricidal lymphocytes are frequently dysfunctional or apoptotic when residing within melanomas and other solid cancers. This phenomenon--tumor-induced immunosuppression--is poorly understood and conceivably limits the efficiency of strategies aiming at activating lymphocyte-mediated antitumor immunity. Recent studies imply that reactive oxygen species (oxygen radicals), produced by tumor-infiltrating monocyte/macrophages, may contribute to the state of lymphocyte inhibition in neoplastic tissue. Histamine, acting via H2-type histamine receptors on monocyte/macrophages, suppresses the activity of a key enzyme in oxygen radical formation, the NADPH oxidase. By this mechanism, histamine protects NK cells and T cells against oxygen radical-induced dysfunction and apoptosis, and also maintains their activation by IL-2 and other lymphocyte activators. In this review, these properties of histamine are discussed in relation to the current use of histamine as an adjunct to IL-2 in metastatic melanoma and other malignant diseases.
Hellstrand
Kristoffer
K
Department of Virology, University of Göteborg, Sweden.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D006632:Histamine / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016233:Immunotherapy, Active; D016219:Immunotherapy, Adoptive; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000502:physiology; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D009000:Monocytes / Q000502:physiology; D017382:Reactive Oxygen Species; D016176:T-Lymphocyte Subsets / Q000502:physiology
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D007376:Interleukin-2; D017382:Reactive Oxygen Species; D006632:Histamine