Friend or Foe? IFNγ Mediates Pro-Metastatic Gene Expression in the Tumor Microenvironment (48.34)
Abstract Several immunotherapeutic models have shown that interferon gamma (IFNγ) is required for tumor regression. Treatment with IFNγ as a sole therapy, however, has resulted in disappointing outcomes. Cytokine therapies, such as IL-2/IL-12 and IL-12/IL-18, each involves IFN-γ mediated reduction i...
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Published in | The Journal of immunology (1950) Vol. 178; no. 1_Supplement; p. S81 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.04.2007
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Online Access | Get full text |
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Summary: | Abstract
Several immunotherapeutic models have shown that interferon gamma (IFNγ) is required for tumor regression. Treatment with IFNγ as a sole therapy, however, has resulted in disappointing outcomes. Cytokine therapies, such as IL-2/IL-12 and IL-12/IL-18, each involves IFN-γ mediated reduction in primary tumors but they can have an unanticipated increase in secondary metastases. Therefore, tumor responsiveness to IFNγ may alter its progression and metastasic potential. Mouse renal carcinoma cells expressing a dominant negative IFNγ-receptor had a reduced ability to metastasize, suggesting that IFNγ may exert potentially pro-metastatic effects in the tumor microenvironment. The goal of this study is to identify changes in gene expression in the tumor microenvironment in response to IFNγ treatment. Using qPCR gene profiling, we identified the increased expression of several pro-metastatic genes specifically in the tumor microenvironment after IFNγ treatment, namely heparanase, CD44, s100a4, and matrix metalloproteinase 7. We are now investigating whether the upregulation of these genes is caused by host and/or tumor responses to IFNγ. Our results suggest that IFNγ regulates extra-cellular matrix remodeling protein expression in the local microenvironment, which may contribute to tumor metastases. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.178.Supp.48.34 |