Direct influences of proinflammatory cytokines (IL-1β, TNF-α, IL-6) on the proliferation and the cell-surface antigen expression of cancer cells

Background: The proinflammatory cytokines, i.e., IL-1, TNF-α and IL-6, produced by surgical intervention or non-specific immunotherapy, may directly affect both the growth and the metastasis of tumor cells. Therefore, it is important to clarify a direct influence of proinflammatory cytokines on tumor cells for better knowledge of anti-tumor therapy. Method: Four human lung cancer cell lines consisting of 2 squamous cell carcinoma and 2 adenocarcinoma were used. Tumor cells were incubated for 72 hours in the presence of various concentrations of each cytokine (IL-1β, TNF-α, IL-6), and the proliferative response was then assessed by MTT assay. After 14 days cultivation with those proinflammatory cytokines, cell-surface antigen expressions (HLA-class I, HLA-class II, CEA, sialyl Le(x)) were assessed by immunocytochemistry. Results: Among various combinations of tumor cells and cytokines, only TNF-α exhibited an antiproliferative effect against PC-9 cells. However, various modulations of cell-surface antigen expression by the cytokines were observed. The HLA-class I antigen expression of PC-9 was augmented by either TNF-α or IL-1β. Furthermore, IL-1β could induce CEA in QG-56, QG-95, and PC-9 cells, while TNF-α could enhance the expression of sialyl Le(x) in QG-95 cells. Conclusion: Although the influence of proinflammatory cytokines on the growth of tumor cells was rare, the modulation of cell-surface antigens was notable. The augmentation of HLA- class I expression can improve immunogenicity of tumor cells while the induction of CEA or sialyl Le(x) can be associated with the promotion of metastasis.