Direct influences of interferon-γ on proliferation and differentiation of cancer cells

In order to clarify the anti-tumor activity of IFN-γ, we investigated the direct influence of IFN-γ on both the growth and cell-surface antigen expression of tumor cells. In the present study, four human lung cancer cell lines were used; two squamous cell lines (QG-56, QG-95) and two adenocarcinoma cell lines (PC-9, PC-12). The proliferation of QG-56 or QG-95 was inhibited by IFN-γ in a dose-dependent manner with about 70% inhibition at 1,000 JRU/ml while that of PC-9 was slightly inhibited with maximally 25% inhibition at 1,000 JRU/ml. The growth of PC-12 was not inhibited at all. After culture in the presence of IFN-γ (200 JRU/ml) for 14-16 days, tumor cells were examined for expression of various antigens, including HLA-class I, HLA-class II, and CEA. In all cell lines but PC-12, 100% of cells expressed HLA-class I after incubation with IFN-γ. Both HLA-class II and CEA were induced in those cell lines. The proportion of HLA-class II-positive cells or that of CEA-positive cells varied among the cell lines. Of the three antigens, the degree of HLA-class II expression paralleled that of growth inhibition by IFN-γ treatment. These results suggested that in various functions of IFN-γ against tumor cells, both the anti-proliferative effect and the induction of HLA-class II might be closely linked together in an intracellular signal transduction.