Direct influences of pro-inflammatory cytokines (IL-1 beta, 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 fact or alpha (TNF-alpha), IL-6 produced by surgical intervention or non-specifi c immunotherapy may directly affect both the growth and the metastasis of t umour cells. It is therefore important to clarify the direct influence of p ro-inflammatory cytokines on tumour cells in order to obtain abetter knowle dge of anti-tumour therapy. Four human lung cancer cell lines were used. Th e tumour cells were incubated for 72 h in the presence of various concentra tions of IL-1 beta, TNF-alpha, or IL-6 and then the proliferative response was assessed by an MTT assay. After 14 days of culture with each pro-inflam matory cytokine, the cell-surface antigen expressions (HLA-class I, HLA-cla ss IT, CEA, sialyl Lewis(x)) were assessed by an immunocytochemical Stainin g method. Among the various combinations of tumour cells (PC-9, PC-12, QG-5 6, QG-95) and cytokines (IL-1 beta, TNF-alpha, IL-6), only TNF-alpha signif icantly 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-1 beta. Furthermore, IL-1 beta was able to induce C EA in PC-9, QG-56; and QG-95 cells while TNF-a was able to enhance the expr ession of sialyl Lewisx in QG-95 cells. Although the influence of pro-infla mmatory cytokines on the growth of tumour cells was only slight, some modul ations of the cell-surface antigen expression were notable. The augmentatio n of HLA-class I expression can thus improve the immunogenicity of tumour c ells while the. induction of CEA or sialyl Lewis(x) may therefore be associ ated with the promotion of metastasis. (C) 2000 Academic Press.