Editors' ChoiceMelanoma

New Kid on the Block

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Science Translational Medicine  18 Jul 2012:
Vol. 4, Issue 143, pp. 143ec125
DOI: 10.1126/scitranslmed.3004589

Effective new therapies are urgently needed for metastatic melanoma, which is almost always fatal. Recent work indicates that immunotherapy—in which the immune response against melanoma is enhanced—represents a promising approach. For example, transfer of tumor-specific T helper (TH) cells, which activate and direct other immune cells, can abolish melanoma in mice; such cells may help limit melanoma growth in humans. Now, work by Purwar et al. indicates that a specific type of TH cell can induce tumor immunity.

The authors’ initial goal was to understand the role of TH17 cells—a TH lineage that secretes the cytokine interleukin 17 (IL-17) and is traditionally associated with autoimmunity—in melanoma progression. The scientists injected melanoma cells into mice deficient for TH17 cells and wild-type controls and observed markedly inhibited tumor growth in the TH17-deficient mice. Transcriptional profiling revealed that IL-9 expression was much higher in TH cells from the TH17-deficient mice versus controls; furthermore, blockade of IL-9 largely reversed the inhibition of tumor growth in the TH17-deficient mice. Transfer of IL-9–producing T cells (TH9 cells) into wild-type mice, which were also injected with melanoma cells, blocked melanoma growth more effectively than other types of TH cells; TH9 cells could also directly induce tumor cell apoptosis. Administration of recombinant IL-9 inhibited melanoma growth in wild-type mice and mice lacking T and B cells but not in mice lacking mast cells, suggesting that the effect of IL-9 is mediated through mast cells. Last, Purwar et al. detected higher levels of TH9 cells and IL-9 in healthy human skin and blood than in metastatic melanoma lesions of patients with advanced disease.

This work reveals IL-9 to be a noteworthy therapeutic candidate for melanoma, but several intriguing questions remain. For example, the precise function of mast cells in mediating antitumor immunity through IL-9 must be explored. Is there a role for IL-9 in preventing melanoma in alternative mouse models that parallel oncogene-driven cancer progression in humans? Additionally, it would be interesting to determine whether IL-9 levels are restored in prior sites of melanoma metastasis that have regressed in the setting of immunotherapy.

R. Purwar et al., Robust tumor immunity to melanoma mediated by interleukin-9–producing T cells. Nat. Med., 8 July 2012 (10.1038/nm.2856). [PubMed]

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