Subversion of immune system by tumor cells and role of prostaglandins.

Mice bearing syngeneic tumors, chemical and virus-induced, became immunologically unresponsive to sheep erythrocytes. The increase in the degree of unresponsiveness with tumor growth suggested a causal relationship. Immunosuppression was in fact caused by the tumor cells because the addition of tumor cells to in vitro cultures of spleen cells and sheep erythrocytes resulted in suppression of antibody response. Suppression was dose dependent with a ratio of 1 to 1000 of tumor cells to spleen cells sufficient to produce significant suppression. Prostaglandins were found to have a role in immunosuppression by tumor cells in that PGE2 was itself immunosuppressive and in that indomethacin and aspirin, inhibitors of prostaglandin synthetases, blocked immunosuppression in vitro and retarded tumor growth in vivo. These findings suggest that tumors, although antigenic, may be able to escape immuno-sureillance by their host by means of subverting the immune system. Thus, success of immunotherapy may well depend on our ability to prevent or block the immunosuppressive activity of tumors.