Adoptive cell therapy (ACT) using melanoma-specific cytotoxic T cells can promote remission in patients with metastatic melanoma, but the tumours often return; this study offers an explanation why. The authors used both mouse and human systems to show that tumour necrosis factor (TNF) promotes the loss of melanoma-associated antigens, such as MART1 or gp100, from melanoma cells. This was a reversible phenomenon, as the melanoma cells reacquired expression of gp100 when transplanted into other hosts. Although the TNF-conditioned melanoma cells could no longer be recognized by T cells specific for melanocytic antigens, they could be targeted by T cells specific for other mutated proteins. Therefore, in future, the efficacy of ACT could be improved by targeting both melanocytic and non-melanocytic antigens.
ORIGINAL RESEARCH PAPER
Landsberg, J. et al. Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature 10 Oct 2012 (doi:10.1038/nature11538)
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Bordon, Y. Inflammation blinds T cells to melanoma. Nat Rev Immunol 12, 747 (2012). https://doi.org/10.1038/nri3338
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DOI: https://doi.org/10.1038/nri3338