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Interleukin-9 (IL-9) is a T cell cytokine that acts through a γC-family receptor on target cells and is associated with inflammation and allergy. We determined that T cells from mice deficient in the T helper type 17 (T_H17) pathway genes encoding retinoid-related orphan receptor γ (ROR-γ) and IL-23 receptor (IL-23R) produced abundant IL-9, and we found substantial growth inhibition of B16F10 melanoma in these mice. IL-9–blocking antibodies reversed this tumor growth inhibition and enhanced tumor growth in wild-type (WT) mice. Il9r^−/− mice showed accelerated tumor growth, and administration of recombinant IL-9 (rIL-9) to tumor-bearing WT and Rag1^−/− mice inhibited melanoma as well as lung carcinoma growth. Adoptive transfer of tumor-antigen–specific T_H9 cells into both WT and Rag1^−/− mice suppressed melanoma growth; this effect was abrogated by treatment with neutralizing antibodies to IL-9 …