Journal article
Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response
The Journal of immunology (1950), Vol.179(2), pp.977-983
07/15/2007
DOI: 10.4049/jimmunol.179.2.977
PMID: 17617589
Abstract
Although the immune system has the potential to protect against malignancies, many individuals with cancer are immunosuppressed. Myeloid-derived suppressor cells (MDSC) are elevated in many patients and animals with tumors, and contribute to immune suppression by blocking CD4(+) and CD8(+) T cell activation. Using the spontaneously metastatic 4T1 mouse mammary carcinoma, we now demonstrate that cross-talk between MDSC and macrophages further subverts tumor immunity by increasing MDSC production of IL-10, and by decreasing macrophage production of IL-12. Cross-talk between MDSC and macrophages requires cell-cell contact, and the IL-12 decrease is dependent on MDSC production of IL-10. Treatment with the chemotherapeutic drug gemcitabine, which reduces MDSC, promotes rejection of established metastatic disease in IL-4Ralpha(-/-) mice that produce M1 macrophages by allowing T cell activation, by maintaining macrophage production of IL-12, and by preventing increased production of IL-10. Therefore, MDSC impair tumor immunity by suppressing T cell activation and by interacting with macrophages to increase IL-10 and decrease IL-12 production, thereby promoting a tumor-promoting type 2 response, a process that can be partially reversed by gemcitabine.
Details
- Title: Subtitle
- Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response
- Creators
- Pratima Sinha - University of Maryland, Baltimore CountyVirginia K Clements - University of Maryland, Baltimore CountyStephanie K Bunt - University of Maryland, Baltimore CountySteven M Albelda - University of PennsylvaniaSuzanne Ostrand-Rosenberg - University of Maryland, Baltimore County
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.179(2), pp.977-983
- DOI
- 10.4049/jimmunol.179.2.977
- PMID
- 17617589
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 07/15/2007
- Academic Unit
- Family and Community Medicine
- Record Identifier
- 9984297339302771
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