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Publication : IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate.

First Author  Le TT Year  2016
Journal  PLoS One Volume  11
Issue  4 Pages  e0153975
PubMed ID  27100888 Mgi Jnum  J:252413
Mgi Id  MGI:6093366 Doi  10.1371/journal.pone.0153975
Citation  Le TT, et al. (2016) IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate. PLoS One 11(4):e0153975
abstractText  Ingenol mebutate is approved for the topical treatment of actinic keratoses and may ultimately also find utility in treating skin cancers. Here we show that relapse rates of subcutaneous B16 melanoma tumours treated topically with ingenol mebutate were not significantly different in C57BL/6 and Rag1-/- mice, suggesting B and T cells do not play a major role in the anti-cancer efficacy of ingenol mebutate. Relapse rates were, however, significantly increased in MyD88-/- mice and in C57BL/6 mice treated with the anti-IL-1 agent, anakinra. Ingenol mebutate treatment induces a pronounced infiltration of neutrophils, which have been shown to have anti-cancer activity in mice. Herein we provide evidence that IL-1 promotes neutrophil recruitment to the tumour, decreases apoptosis of infiltrating neutrophils and increases neutrophil tumour killing activity. These studies suggest IL-1, via its action on neutrophils, promotes the anti-cancer efficacy of ingenol mebutate, with ingenol mebutate treatment causing both IL-1beta induction and IL-1alpha released from keratinocytes.
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