Switching on the macrophage-mediated suppressor mechanism by tumor cells to evade host immune surveillance

The present study demonstrates a unique mechanism for tumor cell-induced immunosuppression. In the presence of a nonsuppressive dose of tumor cells, generation of cytotoxic T cells in the mixed lymphocyte culture (MLC) is completely suppressed by adding exogenous (peritoneal) macrophages (PM phi) after the initiation of the MLC. This indicates that tumor cells can switch on a suppressor mechanism through host macrophages. It has further been determined that suppression can be induced only if resident (splenic) macrophages (SM phi) are exposed to tumor cells prior to addition of PM phi. If SM phi and PM phi are simultaneously present with the tumor cells, induction of suppression is completely precluded. These findings indicate that switching on of the suppressor mechanism by tumor cells has a critical requirement for the collaboration of two populations of macrophages, SM phi and PM phi, and their presence in a specific sequence (SM phi preceding PM phi). This may represent one of the mechanisms by which tumor cells evade host immune surveillance.