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IL-15 deficient Tax mice reveal a role for IL-1α in tumor immunity
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ORAL PRESENTATION Open Access IL-15 deficient Tax mice reveal a role for IL-1a in tumor immunity Daniel A Rauch, John C Harding, Lee Ratner * From 16th International Conference on Human Retroviruses: HTLV and Related Viruses Montreal, Canada. 26-30 June 2013 IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a pro- moter of cancer and a promoter of anti-cancer immu- nity. 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 devel- opment 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 acceler- ated 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-1a and IL-1a-regulated cytokines. Moreover, anti-IL-1a antibodies and an IL-1 receptor antagonist (Anakinra) were used to interrogate the potential of IL-1a targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1a as therapeutic targets in lymphoma. Published: 7 January 2014 doi:10.1186/1742-4690-11-S1-O11 Cite this article as: Rauch et al.: IL-15 deficient Tax mice reveal a role for IL-1a in tumor immunity. Retrovirology 2014 11(Suppl 1):O11. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit * Correspondence: [email protected] Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA Rauch et al. Retrovirology 2014, 11(Suppl 1):O11 http://www.retrovirology.com/content/11/S1/O11 © 2014 Rauch et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Transcript of IL-15 deficient Tax mice reveal a role for IL-1α in tumor immunity
ORAL PRESENTATION Open Access
IL-15 deficient Tax mice reveal a role for IL-1a intumor immunityDaniel A Rauch, John C Harding, Lee Ratner*
From 16th International Conference on Human Retroviruses: HTLV and Related VirusesMontreal, Canada. 26-30 June 2013
IL-15 is recognized as a promising candidate for tumorimmunotherapy and has been described as both a pro-moter of cancer and a promoter of anti-cancer immu-nity. IL-15 was discovered in cells transformed byHTLV-1, the etiologic agent of adult T cell leukemia /lymphoma (ATL) and the human retrovirus that carriesthe Tax oncogene. We have developed the TAX-LUCmouse model of ATL in which Tax expression drivesboth malignant transformation and luciferase expression,enabling non-invasive imaging of tumorigenesis in realtime. To identify the role of IL-15 in spontaneous devel-opment of lymphoma in vivo, an IL-15-/- TAX-LUCstrain was developed and examined. The absence ofIL-15 resulted in aggressive tumor growth and acceler-ated mortality and demonstrated that IL-15 was notrequired for Tax-mediated lymphoma but was essentialfor anti-tumor immunity. Further analysis revealed aunique transcriptional profile in tumor cells that arise inthe absence of IL-15 that included a significant increasein the expression of IL-1a and IL-1a-regulated cytokines.Moreover, anti-IL-1a antibodies and an IL-1 receptorantagonist (Anakinra) were used to interrogate thepotential of IL-1a targeted therapies in this model.Taken together, these findings identify IL-15 and IL-1aas therapeutic targets in lymphoma.
Published: 7 January 2014
doi:10.1186/1742-4690-11-S1-O11Cite this article as: Rauch et al.: IL-15 deficient Tax mice reveal a rolefor IL-1a in tumor immunity. Retrovirology 2014 11(Suppl 1):O11.
Submit your next manuscript to BioMed Centraland take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at www.biomedcentral.com/submit
* Correspondence: [email protected] of Medicine, Washington University School of Medicine, St.Louis, Missouri, USA
Rauch et al. Retrovirology 2014, 11(Suppl 1):O11http://www.retrovirology.com/content/11/S1/O11
© 2014 Rauch et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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