| First Author | Rauch DA | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 1 | Pages | e85028 |
| PubMed ID | 24416335 | Mgi Jnum | J:229653 |
| Mgi Id | MGI:5752726 | Doi | 10.1371/journal.pone.0085028 |
| Citation | Rauch DA, et al. (2014) IL-15 deficient tax mice reveal a role for IL-1alpha in tumor immunity. PLoS One 9(1):e85028 |
| abstractText | 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-1alpha and IL-1alpha-regulated cytokines. Moreover, anti-IL-1alpha antibodies and an IL-1 receptor antagonist (Anakinra) were used to interrogate the potential of IL-1alpha targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1alpha as therapeutic targets in lymphoma. |
