Suppressor macrophages in tumor-bearing mice and their selective inhibition by 6-mercaptopurine.

Using the in vitro polyclonal blastogenesis test, we identified peritoneal suppressor cells from L1210 leukemia-bearing mice as Ia-negative macrophages. These cells manifested adherence to plastic tubes and sensitivity to silica but not to X-irradiation and treatment with alpha Thy 1.2 or alpha Ia 7 antibody plus complement. The suppressor activity of peritoneal macrophages was detected as early as 3 days after L1210 inoculation; however, the number of suppressor macrophages did not increase until Day 7. 6-Mercaptopurine (6-MP) inhibited their suppressor activity, whereas three other antineoplastic agents, including cyclophosphamide, did not. 6-MP-dependent suppressor inhibition was induced irrespective of whether treatment was combined with tumor vaccine. In vitro, the sensitivity of suppressor macrophages to 6-MP was not enhanced. This and the finding that 6-MP induced an increase rather than a decrease in the number of peritoneal macrophages indicated that, in vivo, 6-MP selectively inhibited suppressor macrophages. The inverse correlation of their suppressor activity and the therapeutic response in tumor-bearing mice administered with tumor vaccine and antineoplastic agents suggests that peritoneal suppressor macrophages were involved in modulating the efficacy of active immunotherapy. This was further substantiated by the finding that the strongly immunosuppressive macrophages of L1210-bearing and cyclophosphamide-treated mice inhibited the antitumor response of L1210 vaccine-primed mice.