Journal article
Inflammation enhances myeloid-derived suppressor cell crosstalk by signaling through Toll-like receptor 4
Journal of leukocyte biology, Vol.85(6), pp.996-1004
06/01/2009
DOI: 10.1189/jlb.0708446
PMCID: PMC2698586
PMID: 19261929
Abstract
Myeloid-derived suppressor cells (MDSC) are potent inhibitors of anti-tumor immunity that facilitate tumor progression by blocking the activation of CD4(+) and CD8(+) T cells and by promoting a type 2 immune response through their production of IL-10 and down-regulation of macrophage production of IL-12. MDSC accumulate in many cancer patients and are a significant impediment to active cancer immunotherapies. Chronic inflammation has been shown recently to enhance the accumulation of MDSC and to increase their suppression of T cells. These findings led us to hypothesize that inflammation contributes to tumor progression through the induction of MDSC, which create a favorable environment for tumor growth. As chronic inflammation also drives type 2 immune responses, which favor tumor growth, we asked if inflammation mediates this effect through MDSC. We find that IL-1 beta-induced inflammation increased IL-10 production by MDSC and induces MDSC, which are more effective at down-regulating macrophage production of IL-12 as compared with MDSC isolated from less-inflammatory tumor microenvironments, thereby skewing tumor immunity toward a type 2 response. Inflammation heightens MDSC phenotype by signaling through the TLR4 pathway and involves up-regulation of CD14. Although this pathway is well-recognized in other myeloid cells, it has not been implicated previously in MDSC function. These studies demonstrate that MDSC are an intermediary through which inflammation promotes type 2 immune responses, and they identify the TLR4 pathway in MDSC as a potential target for down-regulating immune suppression and promoting anti-tumor immunity. J. Leukoc. Biol. 85: 996-1004; 2009.
Details
- Title: Subtitle
- Inflammation enhances myeloid-derived suppressor cell crosstalk by signaling through Toll-like receptor 4
- Creators
- Stephanie K. Bunt - University of Maryland, Baltimore CountyVirginia K. Clements - University of Maryland, Baltimore CountyErica M. Hanson - University of Maryland, Baltimore CountyPratima Sinha - University of Maryland, Baltimore CountySuzanne Ostrand-Rosenberg - University of Maryland, Baltimore County
- Resource Type
- Journal article
- Publication Details
- Journal of leukocyte biology, Vol.85(6), pp.996-1004
- Publisher
- Wiley
- DOI
- 10.1189/jlb.0708446
- PMID
- 19261929
- PMCID
- PMC2698586
- ISSN
- 0741-5400
- eISSN
- 1938-3673
- Number of pages
- 9
- Grant note
- R01 CA084232; R01 CA115880 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01CA084232 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 06/01/2009
- Academic Unit
- Family and Community Medicine
- Record Identifier
- 9984297351002771
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