Tumor cell-triggered macrophage-mediated suppression of the T-cell cytotoxic response to tumor-associated antigens. II. Mechanisms for induction of suppression.

The mechanisms were investigated for the tumor cell-triggered macrophage-induced suppression of T-cell-mediated tumor immunity. Interaction between tumor cells and macrophages triggered the production of prostaglandin(s) (PG) that initiated the suppressor events. In our experiments, PGE1 or PGE2 suppressed the generation of cytotoxic T-lymphocytes in the syngeneic mixed lymphocyte tumor cell cultures. Indomethacin, a PG synthetase inhibitor, blocked the induction of the macrophage-mediated suppression, which suggested that suppression was caused by endogenous PG. This suppression might be further mediated by the generation of suppressor T-cells. Significant reduction in the levels of macrophage-induced suppression was seen in hosts receiving cyclophosphamide treatment, which could eliminate the precursors of suppressor T-cells. These findings indicated that tumor cells may trigger a chain of reactions, through the generation of suppressor factors or suppressor cells, to subvert the host's immune surveillance.