A possible role of prostaglandins in the inhibition of natural and antibody-dependent cell-mediated cytotoxicity against tumor cells
Droller, M.J.; Schneider, M.U.; Perlmann, P.
Cellular Immunology 39(1): 165-177
Certain tumor cell lines in tissue culture produced prostaglandins and increased production occurred when the tumor cells were exposed to lymphocytes. The present experiments tested the effect of prostaglandins E1 and E2 on natural and antibody-dependent lymphocyte cytotoxicity against the same target cells to determine whether the production of prostaglandins by the tumor cells might influence the efficacy of the cellular immune response. Target cell lines T24 and HCV29 [human bladder] were labeled with 51Cr and incubated at 37.degree. C for various times with lymphocytes prepared from venous blood of normal donors. Antiserum to T24 and varying concentrations of prostaglandin E1 or E2 were added to the samples prior to incubation. In some experiments, lymphocytes or labeled target cells were preincubated with prostaglandins and then washed prior to their addition to the assay tubes. Cytotoxicity was determined by measuring the release of 51Cr from the target cells after incubation. Both prostaglandins inhibited natural and antibody-dependent lymphocyte cytotoxicity against the target cells. The effect appeared to represent a direct one on lymphocytes, and it was amplified by the presence of theophylline in the medium. Inhibition could be effected early on in lymphocyte/target cell interaction, and only a short exposure of lymphocytes to prostaglandins was required for the effect to be manifested. The production of prostaglandins by tumor cells may constitute a means by which the tumor cells subvert the effect of a cellular immune response that is directed against them.