Direct influences of pro-inflammatory cytokines (IL-1beta, TNF-alpha, IL-6) on the proliferation and cell-surface antigen expression of cancer cells.

Pro-inflammatory cytokines, e.g. interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-alpha), IL-6 produced by surgical intervention or non-specific immunotherapy may directly affect both the growth and the metastasis of tumour cells. It is therefore important to clarify the direct influence of pro-inflammatory cytokines on tumour cells in order to obtain a better knowledge of anti-tumour therapy. Four human lung cancer cell lines were used. The tumour cells were incubated for 72 h in the presence of various concentrations of IL-1beta, TNF-alpha, or IL-6 and then the proliferative response was assessed by an MTT assay. After 14 days of culture with each pro-inflammatory cytokine, the cell-surface antigen expressions (HLA-class I, HLA-class II, CEA, sialyl Lewis(x)) were assessed by an immunocytochemical staining method. Among the various combinations of tumour cells (PC-9, PC-12, QG-56, QG-95) and cytokines (IL-1beta, TNF-alpha, IL-6), only TNF-alpha significantly exhibited an antiproliferative effect against PC-9 cells. However, various modulations of the cell-surface antigen expression by the cytokines were observed. The HLA-class I antigen expression of PC-9 was augmented by either TNF-alpha or IL-1beta. Furthermore, IL-1beta was able to induce CEA in PC-9, QG-56, and QG-95 cells while TNF-alpha was able to enhance the expression of sialyl Lewis(x)in QG-95 cells. Although the influence of pro-inflammatory cytokines on the growth of tumour cells was only slight, some modulations of the cell-surface antigen expression were notable. The augmentation of HLA-class I expression can thus improve the immunogenicity of tumour cells while the induction of CEA or sialyl Lewis(x)may therefore be associated with the promotion of metastasis. Copyright 2000 Academic Press.