Reduced Inflammation in the Tumor Microenvironment Delays the Accumulation of Myeloid-Derived Suppressor Cells and Limits Tumor Progression

dc.contributor.authorBunt, Stephanie
dc.contributor.authorYang, Linglin
dc.contributor.authorSinha, Pratima
dc.contributor.authorClements,  Virginia K.
dc.contributor.authorLeips, Jeff
dc.contributor.authorOstrand-Rosenberg, Suzanne
dc.date.accessioned2023-08-07T20:40:02Z
dc.date.available2023-08-07T20:40:02Z
dc.date.issued2007-10-17
dc.description.abstractChronic inflammation is frequently associated with malignant growth and is thought to promote and enhance tumor progression, although the mechanisms which regulate this relationship remain elusive. We reported previously that interleukin (IL)-1β promoted tumor progression by enhancing the accumulation of myeloid-derived suppressor cells (MDSC), and hypothesized that inflammation leads to cancer through the production of MDSC which inhibit tumor immunity. If inflammation-induced MDSC promote tumor progression by blocking antitumor immunity, then a reduction in inflammation should reduce MDSC levels and delay tumor progression, whereas an increase in inflammation should increase MDSC levels and hasten tumor progression. We have tested this hypothesis using the 4T1 mammary carcinoma and IL-1 receptor (IL-1R)–deficient mice which have a reduced potential for inflammation, and IL-1R antagonist–deficient mice, which have an increased potential for inflammation. Consistent with our hypothesis, IL-1R–deficient mice have a delayed accumulation of MDSC and reduced primary and metastatic tumor progression. Accumulation of MDSC and tumor progression are partially restored by IL-6, indicating that IL-6 is a downstream mediator of the IL-1β–induced expansion of MDSC. In contrast, excessive inflammation in IL-1R antagonist–deficient mice promotes the accumulation of MDSC and produces MDSC with enhanced suppressive activity. These results show that immune suppression by MDSC and tumor growth are regulated by the inflammatory milieu and support the hypothesis that the induction of suppressor cells which down-regulate tumor immunity is one of the mechanisms linking inflammation and cancer. [Cancer Res 2007;67(20):10019–26]en_US
dc.description.sponsorshipNIH grants R01 CA115880 and R01 CA84232, and Susan G. Komen for the Cure grant BCTR0503885 (S. Ostrand-Rosenberg); and Department of Defense Breast Cancer Research Program Predoctoral Fellowship W81XWH-05-1-0276 (S.K. Bunt).en_US
dc.description.urihttps://aacrjournals.org/cancerres/article/67/20/10019/533542/Reduced-Inflammation-in-the-Tumor-Microenvironmenten_US
dc.format.extent20 pagesen_US
dc.genrejournal articlesen_US
dc.genrepostprintsen_US
dc.identifierdoi:10.13016/m2mrb1-h6sj
dc.identifier.citationStephanie K. Bunt, Linglin Yang, Pratima Sinha, Virginia K. Clements, Jeff Leips, Suzanne Ostrand-Rosenberg; Reduced Inflammation in the Tumor Microenvironment Delays the Accumulation of Myeloid-Derived Suppressor Cells and Limits Tumor Progression. Cancer Res 15 October 2007; 67 (20): 10019–10026. https://doi.org/10.1158/0008-5472.CAN-07-2354en_US
dc.identifier.urihttps://doi.org/10.1158/0008-5472.CAN-07-2354
dc.identifier.urihttp://hdl.handle.net/11603/29109
dc.language.isoen_USen_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.relation.ispartofUMBC Student Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.en_US
dc.titleReduced Inflammation in the Tumor Microenvironment Delays the Accumulation of Myeloid-Derived Suppressor Cells and Limits Tumor Progressionen_US
dc.typeTexten_US
dcterms.creatorhttps://orcid.org/0000-0002-0850-7821en_US
dcterms.creatorhttps://orcid.org/0000-0002-4492-4390en_US
dcterms.creatorhttps://orcid.org/0000-0001-8999-6630en_US
dcterms.creatorhttps://orcid.org/0000-0002-2095-9732en_US

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