Immunoadjuvant effects of Blastomyces dermatitidis against EL 4 lymphoma in C57BL/6J mice

The ability of thimerosal-killed Blastomyces dermatitidis yeast cells, which greatly enhance the cell-mediated immune response in C57BL/6J mice, to act as an immunopotentiator against EL 4 lymphoma was investigated. Mice treated with yeast cells were protected from as many as 10(4) tumor cells. Complete suppression of tumor growth was observed in treated animals that received ip injections of 10(2) or 10(3) tumor cells. The mice, however, were not immune to further EL 4 lymphoma cell challenge. The lack of tumor-specific immunity indicated nonspecific suppression of tumor growth probably by macrophages. Ten days after treatment, the peritoneal macrophages from mice that showed complete tumor suppression were tested for their ability to prevent in vitro tumor cell proliferation. These macrophages demonstrated 90% inhibition of [3H]thymidine incorporation by EL 4 tumor cells at a 100:1 effector-to-target cell ratio. Macrophages from B. dermatitidis-treated animals exhibited a twofold increase in specific lysis of EL 4 at 10 and 15 days compared to resident macrophages. Spleen and lymph node cells from protected animals showed no cytotoxic activity against EL 4 in a 51Cr release assay. Treatment of tumor-bearing mice with a single dose of B. dermatitidis was effective only if administered within 24 hours of tumor establishment. These results demonstrated that nonviable B. dermatitidis prohibits the growth of EL 4 under conditions where Corynebacterium parvum fails to do so.