The Effect of Prostaglandin and its Inhibitor on the Antibody - dependent Cellular Cytotoxicity Against Human Squamous Cell Carcinoma of the Head and Neck

Lee, Seung Ju; Kim, Chun Dong; Chang, Keun Ho; Kim, Kwang Hyun; Yoon, Seong Jun; Lee, Sang Goo; Lee, Hyun Joo; Heo, Dae Seog; Sung, Myung Whun

Abstract

The effects of chimeric monoclonal antibodies (cMAbs), prostaglandin E, (PGE,), and indomethacin (INDO) on antibody-dependent cellular cytotoxicity (ADCC) against human squamous cell carcinoma of head and neck (SCCHN) cell line were examined. Using the PCI-50 SCCHN cell line as target and normal human peripheral blood mononuclear cells as effector, ADCC was enhanced by the treatment of cMAbs (1.25 p,g/ml), but was inhibited by exogenous PGE (5 X 10' M). The effects of cMAb and PGE were dose-dependent. Maximal suppression of activity occured when PGE was present during the entire 4-hr 'Cr-release assay period, whereas pretreatment of effector cells with PGE had minimal inhibitory effect after washing. These results indicate that decreased ADCC seen with SCCHN targets treated with PGE is related to post-binding events, such as binding of effector and target cells. Pre-treatment of effector cells with INDO (1 ug/ml) resulted in restoration of NK activity which was inhibited by PGE. Our in vitro results suggest that INDO can increase tumor cell killing by the reversal of the suppression for many imrnune functions by PGE.