Robust tumor immunity to melanoma mediated by interleukin 9

Interleukin-9 is a T cell cytokine that acts through a γC-family receptor on target cells. We determined that T cells from mice deficient in the T(H)17 pathway genes ROR-γ and IL-23R produced abundant IL-9, and observed significant growth inhibition of B16F10 melanoma tumor in these mice. IL-9 blocking antibodies reversed this tumor growth inhibition, and enhanced tumor growth in normal mice. IL9R(−/−) mice showed accelerated tumor growth, while administration of rIL-9 to tumor bearing mice inhibited tumor growth. Adoptive transfer of tumor antigen-specific T(H)9 cells blocked tumor growth; this was reversed by anti-IL-9. Exogenous rIL-9 inhibited tumor growth in Rag1(−/−) mice, but not in mast cell deficient mice, suggesting a T cell independent process. Finally, we found T(H)9 cells in normal human skin and blood, and low IL-9 production from melanoma tumor infiltrating lymphocytes. These results suggest a role for IL-9 in tumor immunity, and suggest therapeutic strategies.