MITOMYCIN C-AUGMENTED PRODUCTION OF I-A ANTIGEN-POSITIVE MACROPHAGES IN TUMOR VACCINE-PRIMED MICE

Abstract

Intraperitoneal inoculation of L1210 murine leukemia cell vaccine increased I-A^d antigen-positive and -negative macrophages in the peritoneal cavity of histocompatible mice. Mitomycin C, a poor producer of I-A^d antigen-positive macrophages, selectively augmented the production of I-A^d antigen-positive macrophages in L1210 vaccine-primed mice, since it did not augment the production of non-macrophage cells. Since our previous study showed that the priming of mice with L1210 vaccine and mitomycin C induced augmented antitumor response, we tested the feasibility of the association of mitomycin C-augmented I-A^d antigen-positive macrophages with the augmented antitumor response. Prostaglandin E₂ suppressed the antitumor response in L1210 vaccine- and mitomycin C-primed mice and, consistent with this, it inhibited the production of I-A^d antigen-positive macrophages, although it inhibited the production of non-macrophage cells as well. This hypothesis was further tested by the use of silica. When L1210 vaccine- and mitomycin C-primed mice were further given silica on the day of and one day after live L1210 inoculation, their antitumor response was strongly suppressed, while a kinetic analysis of the cellularity of peritoneal cells showed that administration of silica resulted in a decrease of I-A^d antigen-positive macrophages, but not I-A^d antigen-negative macrophages or non-macrophage cells in these mice. These results strongly suggest, though they do not prove, the association of mitomycin C-augmented production of I-A^d antigen-positive macrophages with the antitumor response in L1210 vaccine- and mitomycin C-primed mice.