Biomedicine

Interfer(on)-ing in Melanoma

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Science  25 Feb 2011:
Vol. 331, Issue 6020, pp. 988-989
DOI: 10.1126/science.331.6020.988-d

Malignant melanoma is a particularly deadly form of skin cancer, for which the major risk factor is exposure to UV solar radiation, especially at a young age. How UV exposure eventually leads to melanoma is not well understood. Using a mouse model of UV light–induced melanoma where melanocytes can be visualized fluorescently, Zaidi et al. find that the cytokine interferon-γ (IFN-γ) is an important driver of tumorigenesis. Gene expression analysis of melanocytes from neonatal mice recently exposed to UV light revealed an IFN gene signature.

After UV exposure, macrophages entered the exposed skin and produced IFN-γ. When these macrophages were isolated and mixed with melanoma cells and then implanted into mice, tumors mixed with macrophages grew faster and exhibited less cell death than did tumor cells implanted without macrophages. These results may be of clinical relevance, because macrophages that expressed IFN-γ were found in tissues from melanoma patients. Melanomas, therefore, may arise in part because of an ineffective immune response to damaged tissue. After UV exposure, the immune system most likely eliminates many of the damaged cells; however, the remaining cells perhaps contain mutations that allow for immune evasion and over time give rise to melanomas.

Nature 469, 548 (2011).

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