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 phagocytes as a defence mechanism against malignant cells. However, these cells 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 the 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 lines, using indirect immunofluorescence and flow cytometry; (3) the sensitivity 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 cell lines liberated soluble factors that inhibited TNF-alpha production in monocytes. This effect occurred even after membrane contact with the A-427 and SK-MES-1 cell lines. Erythroleukaemia K-562 cells expressed both types of 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-427 and K-562 were insensitive to the cytotoxic action of rhTNF-alpha. In conclusion, different lung cancer cell lines may evade destruction by TNF-alpha by various mechanisms that range from blocking TNF-alpha production by monocytes to blocking the cytotoxic action of this molecule. For selecting the most effective immunotherapy, knowledge of the evasion mechanisms would be useful.
López-González
J S
JS
Departamento de Enfermedades Crónico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico.
Hernández García
A
A
Noyola
M I
MI
Cázares
D A
DA
Mandoki
J J
JJ
Morales
F M
FM
Mendieta
I C
IC
Caloca
J V
JV
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology; D018920:Coculture Techniques; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000473:pathology; D009000:Monocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha