Title |
IL-10 Immunomodulation of Myeloid Cells Regulates a Murine Model of Ovarian Cancer
|
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Published in |
Frontiers in immunology, January 2011
|
DOI | 10.3389/fimmu.2011.00029 |
Pubmed ID | |
Authors |
Kevin M. Hart, Katelyn T. Byrne, Michael J. Molloy, Edward M. Usherwood, Brent Berwin |
Abstract |
Elevated levels of IL-10 in the microenvironment of human ovarian cancer and murine models of ovarian cancer are well established and correlate with poor clinical prognosis. However, amongst a myriad of immunosuppressive factors, the actual contribution of IL-10 to the ovarian tumor microenvironment, the mechanisms by which it acts, and its possible functional redundancy are unknown. We previously demonstrated that elimination of the myeloid-derived suppressor cell (MDSC) compartment within the ovarian tumor ascites inhibited tumor progression and, intriguingly, significantly decreased local IL-10 levels. Here we identify a novel pathway in which the tumor-infiltrating MDSC are the predominant producers of IL-10 and, importantly, require it to develop their immunosuppressive function in vivo. Importantly, we demonstrate that the role of IL-10 is critical, and not redundant with other immunosuppressive molecules, to in vivo tumor progression: blockade of the IL-10 signaling network results in alleviation of MDSC-mediated immunosuppression, altered T cell phenotype and activity, and improved survival. These studies define IL-10 as a fundamental modulator of both MDSC and T cells within the ovarian tumor microenvironment. Importantly, IL-10 signaling is shown to be necessary to the development and maintenance of a permissive tumor microenvironment and represents a viable target for anti-tumor strategies. |
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Geographical breakdown
Country | Count | As % |
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United States | 1 | 1% |
Unknown | 82 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 23 | 28% |
Researcher | 9 | 11% |
Student > Bachelor | 9 | 11% |
Student > Master | 6 | 7% |
Student > Doctoral Student | 4 | 5% |
Other | 13 | 16% |
Unknown | 19 | 23% |
Readers by discipline | Count | As % |
---|---|---|
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Biochemistry, Genetics and Molecular Biology | 16 | 19% |
Medicine and Dentistry | 9 | 11% |
Immunology and Microbiology | 9 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
Other | 4 | 5% |
Unknown | 26 | 31% |