IL-9 and T_H9 Cells Confer Tumor Immunity

Adoptive transfer of T cells has been used effectively to treat melanoma patients, but the role of specific subsets of effector T cells in tumor immunity is not well understood. Purwar and colleagues demonstrate that T-helper type 9 (T_H9) cells and production of interleukin (IL)-9, a T-cell cytokine, mediate solid tumor immunity. Mice deficient for another subset of T-helper cells, T_H17, exhibited reduced growth of subcutaneous melanoma tumors and increased T-cell tumor infiltration compared with wild-type control animals. Transcriptional profiling of these infiltrating T cells identified Il9 as one of the most highly upregulated genes. Treatment with IL-9–neutralizing antibodies or the absence of IL-9 receptor expression accelerated tumor growth, indicating that tumor inhibition requires IL-9 signaling. Conversely, treatment with recombinant IL-9 (rIL-9) suppressed both melanoma and lung carcinoma growth in wild-type mice and prolonged survival, suggesting that administration of rIL-9 has a protective effect against tumor progression. Among the different effector T-cell subsets, adoptive transfer of T_H9 cells showed the strongest reduction in melanoma tumor growth and induced melanoma cell apoptosis in vitro, and this inhibitory effect was mediated in part through IL-9 signaling. In addition, rIL-9–stimulated tumor resistance was dependent on the presence of mast cells, but not B or T cells. Interestingly, IL-9–secreting T_H9 cells were detected in normal human peripheral blood and skin but were present in fewer numbers in tumor-infiltrating lymphocytes from patients with metastatic melanoma. These results support a role for IL-9 and T_H9 cells in tumor immunity and suggest a strategy for the treatment of melanoma.

Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, et al. Robust tumor immunity to melanoma mediated by interleukin-9–producing T cells. Nat Med 2012 July 8 [Epub ahead of print].