Tumor cells secreting IL-13 but not IL-13Ralpha2 fusion protein have reduced tumorigenicity in vivo.
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-13Ralpha2, may act as a decoy receptor for IL-13. The anti-tumor effect of IL-13 and its soluble receptor IL-13Ralpha2 have been examined in different tumor systems. Previous studies have shown that IL-13 enhances anti-tumor responses in some model systems, whereas IL-13Ralpha2Fc 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-13Ralpha2Fc 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-13Ralpha2Fc gene transduction nor in vivo treatment with soluble IL-13Ralpha2Fc has a statistically significant effect of tumor growth. IL-13Ralpha2 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-13Ralpha2, has anti-tumor activity in the models described here, possibly by enhancing innate anti-tumor immunity.
Ma
Hak-Ling
HL
Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
Whitters
Matthew J
MJ
Jacobson
Bruce A
BA
Donaldson
Deborah D
DD
Collins
Mary
M
Dunussi-Joannopoulos
Kyriaki
K
D000818:Animals; D045744:Cell Line, Tumor / Q000637:transplantation; D005354:Fibrosarcoma / Q000276:immunology* / Q000628:therapy; D015316:Genetic Therapy; D018793:Interleukin-13 / Q000276:immunology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D008264:Macrophages / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D053660:Receptors, Interleukin-13; D013601:T-Lymphocytes / Q000276:immunology*
C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D009363:Neoplasm Proteins; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13