Robust tumor immunity to melanoma mediated by interleukin-9–producing T cells

Abstract

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 TH17 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 TH9 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 TH9 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.