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-gamma (IFN-gamma) is of particular relevance. IFN-gamma 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-gamma seems to be critically involved.