The effect of prostaglandin and its inhibitor on antibody-dependent cellular cytotoxicity against human squamous cell carcinoma of head and neck.

The effects of chimeric monoclonal antibodies (cMAbs), prostaglandin E2(PGE2), 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 the effector, ADCC was enhanced by the treatment of cMAbs (1.25 micrograms/ml), but was inhibited by exogenous PGE2(5 x 10-7M). The effects of cMAb and PGE2 were dose-dependent. Maximal suppression of activity occurred when PGE2 was present during the entire 4 hour 51Cr-release assay period, whereas pretreatment of effector cells with PGE2 had minimal inhibitory effect after washing. These results indicate that decreased ADCC seen with SCCHN targets treated with PGE2 is related to post-binding events, such as binding of effector and target cells. Pre-treatment of effector cells with INDO (1 microgram/ml) resulted in restoration of NK activity which was inhibited by PGE2. Our in vitro results suggest that INDO can increase tumor cell killing by the reversal of the suppression for many immune functions by PGE2.