Gerald Brandacher, Christiana Winkler, Katharina Schroecksnadel, Raimund Margreiter and Dietmar Fuchs Pages 599 - 612 ( 14 )
Insufficient immunosurveillance is an important aspect in early tumorigenesis and in the pathogenesis of malignant disease. In the later course of cancer, the development of immunodeficiency is considered the major reason for disease progression and death. Within the anti-tumoral host defense reaction, Th1-type cytokine interferon-γ (IFN-γ) is of particular relevance. IFN-γ stimulates several anti-proliferative and thus tumoricidal biochemical pathways in macrophages and other cells and also in tumor cell lines. These include inducible nitric oxide synthase, indoleamine (2, 3)- dioxygenase, an enzyme degrading the essential amino acid tryptophan, and the production of reactive oxygen species and neopterin in human macrophages and dendritic cells. Although the anti-proliferative strategy of the immune system aims to inhibit the growth of malignant cells, it can also affect T-cell response and thus contribute to the development of immunodeficiency. Accelerated degradation of tryptophan and increased production of neopterin were found to parallel the course of malignant diseases. Moreover, a higher degree of these metabolic changes characterizes poor prognosis and is associated with the development of anemia, weight loss and depressive mood in patients. Available data suggest that immunodeficiency in cancer patients may develop as a long-term side-effect of the antiproliferative and pro-apoptotic mechanisms elicited within Th1-type immune response, and enhanced production of pro-inflammatory cytokine IFN-γ seems to be critically involved.
Interferon-γ, cancer, immunodeficiency, indoleamine 2, 3-dioxygenase
Division of Biological Chemistry, Biocenter Innsbruck Medical University, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria.