Evasion mechanisms to tumor necrosis factor alpha (TNF-alpha) of small cell lung carcinoma and non-small cell lung carcinoma cell lines: comparison with the erythroleukaemia K-562 cell line

The tumour necrosis factor alpha (TNF-alpha) is produced by mononuclear pha gocytes as a defence mechanism against malignant cells. However, these cell s can evade destruction by TNF-alpha. The present study evaluates in three lung cancer cell lines (small cell carcinoma NCI-H69, adenocarcinoma A-427, squamous carcinoma SK-MES-1) and one erythroleukaemia (K-562) cell line th e following evasion mechanisms: (1) inhibition of TNF-alpha production, in indirect and direct co-cultures with monocytes; (2) the expression of type I and type II receptors for TNF-alpha (TNFRI and TNFRII) by tumour cell lin es, using indirect immunofluorescence and flow cytometry; (3) the sensitivi ty of tumour cell lines to the toxic action of recombinant human TNF-alpha (rhTNF-alpha). With the exception of cell line NCI-H69, the other tumour ce ll lines liberated soluble factors that inhibited TNF-alpha production in m onocytes. This effect occurred even after membrane contact with the A-427 a nd SK-MES-1 cell lines. Erythroleukaemia K-567 cells expressed both types o f receptors for TNF-alpha, whereas the NCI-H69 cells expressed only TNFRI, and the A-427 and SK-MES-1 cells expressed no receptors. Lines NCI-H69, A-4 27 and K-562 were insensitive to the cytotoxic action of rhTNF-alpha. In co nclusion, different lung cancer cell lines may evade destruction by TNF-alp ha by various mechanisms that range from blocking TNF-alpha production by m onocytes to blocking the cytotoxic action of this molecule. For selecting t he most effective immunotherapy, knowledge of the evasion mechanisms would be useful. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.