SECRETION OF BOTH IL-2 AND IL-4 BY TUMOR-CELLS RESULTS IN REJECTION AND IMMUNITY

The generation of a therapeutic immune response to malignancy is criti cally dependent on the inherent immunogenicity of the tumor. Our study demonstrates that secretion of both interleukin-2 (IL-2) and IL-4 by a seemingly nonimmunogenic tumor abrogates tumorigenicity, and mice th at have rejected the genetically modified tumor are immune to challeng es with the parental tumor. The induction of immunity by the IL-2/IL-4 -secreting tumor was significantly better than that achieved with the admixture of tumor cells and the classic adjuvant, Corynebacterium par vum. To elicit a primary immune response, the majority of cells needed to secrete both cytokines. Admixture of IL-2-secreting cells with IL- 4-secreting cells did not result in tumor cell rejection. The IL-2/IL- 4-secreting tumor cells were efficiently rejected in animals immunosup pressed by total body irradiation. Depletion of CD4(+) or CD8(+) T cel ls did not abrogate rejection of the tumor cells, but the animals depl eted of CD4 cells failed to generate protective immunity. Our study de monstrates that secretion of the combination of IL-2 and IL-4 signific antly enhances tumor immunogenicity. The requirement of cells secretin g both cytokines suggests an intricate mechanism different from the me re presence of both cytokines at the tumor-inoculation site.