Abstract
IL‐13 is a Th2 cytokine that plays crucial roles in the pathophysiology of allergy, asthma and helminth infection. The high affinity receptor for IL‐13, IL‐13Rα2, may act as a decoy receptor for IL‐13. The anti‐tumor effect of IL‐13 and its soluble receptor IL‐13Rα2 have been examined in different tumor systems. Previous studies have shown that IL‐13 enhances anti‐tumor responses in some model systems, whereas IL‐13Rα2Fc prevents IL‐13 mediated suppression of tumor immuno‐surveillance in a different model system. In this study, we have used a cytokine (receptor) gene therapy approach and studied the immune responses mediated by IL‐13 and IL‐13Rα2Fc in poorly immunogenic B16F1 melanoma and immunogenic MethA fibrosarcoma tumor models. We find that IL‐13 reduces the tumorigenicity of B16F1 melanoma and MethA fibrosarcoma cells in vivo, most likely through the recruitment of neutrophils and macrophages. IL‐13 mediated anti‐tumor responses do not lead to the generation of tumor‐specific T cells. Neither IL‐13Rα2Fc gene transduction nor in vivo treatment with soluble IL‐13Rα2Fc has a statistically significant effect of tumor growth. IL‐13Rα2 deficient host background does not alter tumor growth, suggesting that endogenous levels of IL‐13 do not contribute to an anti‐tumor response in these models. We conclude that IL‐13, but not soluble IL‐13Rα2, has anti‐tumor activity in the models described here, possibly by enhancing innate anti‐tumor immunity.