Identification of IL-9 antitumor activity in melanoma

By Ingrid Grasmo

High expression of interleukin (IL)-9 in immune cells inhibits growth of melanoma, show study findings suggesting a role for this T-cell cytokine in tumor suppression.

"Immunotherapy of cancer is coming of age, and there have been exciting recent results in patients with melanoma treated with drugs that stimulate the immune system," said lead study author Thomas Kupper (Harvard Medical School, Boston, Massachusetts, USA) in a press release.

He added: "We hope that our results will also translate to the treatment of melanoma patients, but much work still needs to be done."

The researchers aimed to assess the role of T-helper (Th)-17 signaling in melanoma immunity, using mice whose T cells were deficient in two IL-17 pathway molecules - retinoid-related orphan receptor (ROR)-γ and IL-23 receptor (IL-23R).

As reported in Nature Medicine, these mice had high levels of IL-9 and had marked growth inhibition of subcutaneous melanomas compared with wild-type mice.

Thus, "blocking the Th17 pathway may have favored the emergence of a previously unappreciated antitumor pathway," says the team.

The study also shows that mice lacking IL-9 had accelerated tumor growth, and administration of recombinant IL-9 to tumor-bearing wild-type mice inhibited melanoma formation and lung cancer growth, but not the growth of lymphoma cells.

Treatment of mice lacking IL-9 with Th-9 - an immune cell expressing IL-9 - had a similar inhibitory effect on tumor growth, and the inhibitory effect could be reversed by treatment with IL-9-blocking antibodies.

The researchers note that exogenous rIL-9 inhibited tumor growth in mice lacking T and B cells, but not in mast-cell-deficient mice, "suggesting that the targets of IL-9 in this setting include mast cells but not T or B cells."

Investigation of their findings in human cells revealed higher numbers of Th-9 cells in normal human skin and blood compared with metastatic lesions of individuals with progressive stage IV melanoma.

Indeed, Th-9 cells were either absent or present at very low levels in human melanoma, which the researchers say is "noteworthy but should be interpreted with caution."

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