Enhanced suppressive capacity of tumor‐infiltrating myeloid‐derived suppressor cells compared with their peripheral counterparts. Issue 5 (23rd September 2013)

• Record Type: Journal Article
• Authors: Maenhout, Sarah K.; Van Lint, Sandra; Emeagi, Perpetua U.; Thielemans, Kris; Aerts, Joeri L.
• Is Part Of: International journal of cancer. Volume 134:Issue 5(2014:Mar. 01)
• Page Start: 1077
• Page End: 1090
• Publication Date: 2013-09-23
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28449
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Although the main site of action for myeloid‐derived suppressor cells (MDSCs) is most likely the tumor microenvironment, so far the study of these cells has been largely restricted to spleen‐derived MDSCs. In this study, we compared the suppressive capacity of splenic and tumor‐derived MDSCs in different subcutaneous mouse tumor models. We investigated which suppressive mechanisms were involved. Finally, we investigated whether MDSCs and regulatory T cells (T<sub>reg</sub>) cooperate in the suppression of T‐cell responses. In all models, splenic granulocytic MDSCs (grMDSC) strongly suppress CD4<sup>+</sup> T‐cell proliferation while the suppressive effect on CD8<sup>+</sup> T cells is less pronounced. Splenic monocytic MDSCs (moMDSC) have a lower suppressive capacity, compared to grMDSC, on both CD4<sup>+</sup> and CD8<sup>+</sup> T‐cell proliferation. Both grMDSC and moMDSC isolated from the tumor have a much stronger suppressive activity compared to MDSCs isolated from the spleen of tumor‐bearing mice, associated with a higher NO<sub>2</sub><sup>−</sup> production by the tumor‐derived moMDSC and arginase activity for both subsets. The expression of CD80 is also elevated on tumor‐derived grMDSC compared with their peripheral counterparts. Direct contact with tumor cells is required for the upregulation of CD80 and CD80<sup>+</sup> MDSCs are more suppressive than CD80<sup>−</sup> MDSCs. Coculture of T<sub>reg</sub> and MDSCs leads to a stronger suppression of CD8<sup>+</sup> T‐cell proliferation compared to the suppression observed by T<sub>reg</sub> or MDSCs alone. Thus, we showed that tumor‐infiltrating MDSCs possess a stronger suppressive capacity than their peripheral counterparts and that various suppressive mechanisms account for this difference.</p> </abstract>