%0 Journal Article
%T IL-15 Deficient Tax Mice Reveal a Role for IL-1¦Á in Tumor Immunity
%A Daniel A. Rauch
%A John C. Harding
%A Lee Ratner
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0085028
%X IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL) and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15£¿/£¿ TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1¦Á and IL-1¦Á-regulated cytokines. Moreover, anti-IL-1¦Á antibodies and an IL-1 receptor antagonist (Anakinra) were used to interrogate the potential of IL-1¦Á targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1¦Á as therapeutic targets in lymphoma.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085028