Retrovirology

, 8:A24 | Cite as

IL-15 deficiency promotes tumor growth in tax transgenic mice

  • Daniel Rauch
  • Sirosh Bokhari
  • John Harding
  • Lee Ratner
Open Access
Meeting abstract

Keywords

Transgenic Mouse Aggressive Tumor Infiltrate Cell Immune Regulation Promote Tumor Growth 

IL-15 is an NFkB activated cytokine with structural similarity to IL-2 that has been implicated as a promoter of ATLL. Proposed mechanisms include; i) establishment of an autocrine loop in tumor cells that express both IL-15 and the IL-15 receptor, ii) IL-15 mediated protection from apoptosis, and iii) IL-15 mediated immune regulation that promotes tumor growth. IL-15 blockade is being considered as a therapeutic approach to HTLV-1 malignancies. To examine the effects of IL-15 deficiency on HTLV-1 malignancy in vivo, we developed IL-15-/- TAX-LUC mice in which firefly luciferase under the HTLV-1 LTR serves as a reporter of Tax expression driven by the granzyme B promoter. Unexpectedly, the absence of IL-15 resulted in a significantly enhanced tumor phenotype in TAX-LUC mice which developed markedly larger, more numerous, and more aggressive tumors. IL-15 deficiency also resulted in severe osteolytic disease, platelet and bone marrow abnormalities. Administration of soluble IL-15 slowed tumor growth in vivo. Characteristics of cell lines derived from IL-15-/- Tax tumors were indistinguishable from tumor cells derived from IL-15+/+ Tax tumors. RNA harvested from malignant and infiltrating cells within tumors indicated that tumor immunity is significantly affected by IL-15 loss. NK and gamma-delta T cells are diminished in tumor infiltrates in the absence of IL-15 and the malignant cells express elevated levels of IL-1alpha. These findings reveal a profound of effect of tumor immunity in TAX malignancies, implicate IL-1alpha as an important factor in the immune response to ATLL, and caution against IL-15 blockade as an ATLL therapy.

Copyright information

© Rauch et al; licensee BioMed Central Ltd. 2011

This article is published under license to 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.

Authors and Affiliations

  • Daniel Rauch
    • 1
  • Sirosh Bokhari
    • 1
  • John Harding
    • 1
  • Lee Ratner
    • 1
  1. 1.Division of Molecular OncologySt LouisUSA

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