Non-small cell lung cancer-derived soluble mediators and prostaglandin E2 enhance peripheral blood lymphocyte IL-10 transcription and protein production.
Studies suggest that IL-10 may contribute to tumor-associated immunosuppression. In the current study we evaluated the capacity of human non-small cell lung cancer (NSCLC) cell lines to induce PBL IL-10 production. We observed a 10- to 100-fold increase in human PBL IL-10 production following exposure to NSCLC cell supernatants. The tumor-induced increase in PBL IL-10 production was partially blocked by pretreatment of the tumors with the PG inhibitor indomethacin. NSCLC lines were found to constitutively produce PGE2. Exogenous PGE2 also induced PBL IL-10 production in a dose- and time-dependent manner. Both PGE2 and NSCLC supernatant-induced PBL IL-10 production were due to an increase in the IL-10 mRNA transcriptional rate. To evaluate the significance of tumor-induced lymphocyte IL-10 production, the capacity of PBL to produce IFN-gamma during culture in tumor supernatants was assessed in the presence of specific anti-IL-10 mAb. We found enhanced PBL IFN-gamma production following anti-IL-10 treatment. These in vitro studies imply that NSCLC-induced PBL IL-10 production may serve to shift the Th1/Th2 cytokine axis at the tumor site and thus inhibit cell-mediated anti-tumor immune responses. These findings identify a mechanism by which lung cancer cells may escape host immune surveillance. We conclude that NSCLC-derived soluble mediators, including PGs, may play an immunoregulatory role through induction of lymphocyte IL-10 production.
Huang
M
M
Department of Medicine, Johnson Comprehensive Cancer Center, University of California-Los Angeles School of Medicine, 90073, USA.
Sharma
S
S
Mao
J T
JT
Dubinett
S M
SM
D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000276:immunology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D016753:Interleukin-10; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015232:Dinoprostone; D007213:Indomethacin