Effect of antineoplastic agents on the induction of suppressor macrophages by concanavalin A-bound tumor vaccine.

The present study was undertaken to identify tumor vaccineinduced suppressor cells and to examine the effect of antineoplastic agents on their production and suppressor activity. Primary and secondary sensitization with concanavalin A (Con A)-bound L1210 murine leukemia cell vaccine induced sup pressor cells in the peritoneal cavity of histocompatible BALB/ c X DBA/2Cr F! mice. These cells phagocytized latex beads and adhered to plastic vessels. Their suppressor cell activity, determined by polyclonal in vitro spleen cell blastogenesis, was abrogated by silica but not by rabbit anti-mouse brain antiserum and complement. This evidence led to the conclusion that the suppressor cells were macrophages. The production of suppressor macrophages depended on both the Con A-free vaccine cells and vaccine-bound Con A molecules since, singly, neither induced the corresponding suppressor cell activity. Although the induced suppressor cells were not abrogated by mitomycin C in vitro and cyclophosphamide in vivo, the increase of peritoneal suppressor cells follow ing the second vaccination and/or their suppressor activity was significantly inhibited by antineoplastic agents including cyclophosphamide, mitomycin C, and 3-[(4-amino-2-methyl-5pyrimidinyl)methyl]-1 -(2-chloroethyl)-1 -nitrosourea hydrochloride. The finding that vinblastine preferentially inhibited the increase of peritoneal suppressor cells suggested that these agents interfered with the proliferation of suppressor cells (and/or their progenitor cells) in response to the second vac cination. The close correlation between the potency of these antineo plastic agents in inhibiting the production of suppressor cells and the induction of enhanced antitumor immunity by Con Abound tumor vaccine supports the feasibility of the proposed combination of chemotherapy and immunotherapy in which antineoplastic agents are dually effective by killing tumor cells and eliminating the vaccine-associated suppressor cells.