NEUTROPHILS BUT NOT EOSINOPHILS ARE INVOLVED IN GROWTH SUPPRESSION OFIL-4-SECRETING TUMORS

Local expression of IL-4 by gene-modified tumor cells increases their immunogenicity by inducing an inflammatory response that is dominated by eosinophils. Eosinophils have been implicated as antitumor effector cells because the application of a granulocyte-depleting Ab inhibited rejection of IL-4 transfected tumors. This Ab did not discriminate be tween eosinophils and neutrophils and, therefore, this experiment coul d not exclude neutrophils as primary effector cells, whereas eosinophi ls were innocent bystander cells in IL-4 transfected tumors. We analyz ed tumor growth suppression and granulocyte infiltration in IL-5-defic ient (IL-5(-/-)) mice that had a deficiency of eosinophils, using two tumor lines (B16-F10 and MCA205) transfected to secrete IL-4. IL-4-exp ressing tumors were at least as efficiently rejected in IL-5(-/-) mice as in wild-type mice, despite an almost complete absence of tumor-inf iltrating eosinophils. However, neutrophils were present in undiminish ed amounts and their depletion partially restored tumor growth. Furthe rmore, the growth of IL-5-secreting tumors was not impaired in either wildtype or IL-5(-/-) mice, even though it induced eosinophilia in bot h mouse strains. These findings demonstrate that eosinophils can be in duced in IL-5(-/-) mice by exogenous IL-5 and argue against a compensa tory effect of neutrophils in the absence of eosinophils. We conclude that 1) infiltration of IL-4 transfected tumors by eosinophils is comp letely IL-5 dependent, 2) eosinophils have no tumoricidal activity, an d 3) neutrophils are responsible, at least in part, for tumor suppress ion.