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Tumor cell-triggered macrophage-mediated suppression of the T-cell cytotoxic response to tumor-associated antigens. I. Characterization of the cell components for induction of suppression.

A tumor cell-triggered macrophage-mediated suppressor mechanism was demonstrated. It suppressed the induction of specific tumor immunity in the syngeneic, primary mixed lymphocyte tumor cell culture reactions. Preexposure of splenic adherent cells (SAC) to syngeneic FBL-3 tumor cells induced complete suppression of the generation of cytotoxic T-cells. The SAC responsible for inducing suppression were consistent with being macrophages. They were resistant to the treatment of anti-Thy-1.2 antibody plus complement and were relatively radioresistant (at least less than or equal to 750 R X-radiation). Adherent cells obtained from lymph nodes or thymuses acted in the same way as SAC. However, preexposure of peritoneal adherent cells to tumor cells failed to induce suppression. In contrast, the simultaneous presence of peritoneal adherent cells with SAC upon exposure to tumor cells prevented the induction of suppression. These peritoneal cells were also consistent with being macrophages. These results confirmed our previous observations obtained with experiments performed in the allogeneic system. An immunoregulatory circuit existed between two subsets of macrophages that were derived from the population of cells in the peritoneal cavity and from spleen, lymph nodes, or thymus. In the presence of tumor cells, these macrophages produced both positive regulation and negative regulation of the T-cell-mediated cytotoxic response against syngeneic tumor cells. The tumor cells may have utilized the host's own immune network to activate the suppressor mechanisms, thus successfully evading the host's immune surveillance.