Human interferon-gamma enhances expression of ganglioside GM2 on human lung cancer cells and their susceptibility for antiganglioside GM2 monoclonal antibody-dependent cellular cytotoxicity

Interferons are known to modulate several cellular functions by the inducti on of various proteins. In this study, we demonstrated that human interfero n-gamma (HuIFN-gamma) enhanced the expression of ganglioside GM2 (GM2), whi ch is a kind of tumor-associated antigen substantially expressed in human l ung cancer and that human lung cancer cells expressing GM2 became more susc eptible to anti-GM2 monoclonal antibody (mAb)-dependent tumor cell killing mediated by human effector cells after HuIFN-gamma treatment. GM2 expressio n on human lung cancer cells treated with or without HuIFN-gamma was measur ed by flow cytometry. The antibody-dependent cellular cytotoxicity (ADCC) a ctivity was assessed by 4-h Cr-51 release assay. HuIFN-gamma enhanced GM2 e xpression on human small-cell lung cancer (SCLC), SBC-3, and human nonsmall -cell lung cancer (NSCLC), A549 cells in a dose-dependent manner. The optim al concentration of HuIFN-gamma was 1000 U/ml. The effect of HuIFN-gamma re ached maximum after 4 days of culture. HuIFN-gamma did not have any effect to enhance the expression of other gangliosides in SBC-3 cells. No other cy tokines used in this study modulated GM2 expression in SBC-3 cells. Anti-GM 2 mAb-dependent ADCC activities induced by lymphocytes and monocytes were m ore potent against IFN-gamma -treated SBC-3 and A549 cells than nontreated cells. Taken together, HuIFN-gamma combined with anti-GM2 mAb may be useful for immunotherapy against GM2-positive human lung cancer.