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Enhanced suppressive capacity of tumor‐infiltrating myeloid‐derived suppressor cells compared with their peripheral counterparts
Author(s) -
Maenhout Sarah K.,
Van Lint Sandra,
Emeagi Perpetua U.,
Thielemans Kris,
Aerts Joeri L.
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28449
Subject(s) - myeloid derived suppressor cell , cd80 , tumor microenvironment , cd8 , spleen , t cell , cancer research , immunology , cytotoxic t cell , downregulation and upregulation , biology , suppressor , medicine , immune system , cancer , cd40 , in vitro , biochemistry , gene
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 reg ) cooperate in the suppression of T‐cell responses. In all models, splenic granulocytic MDSCs (grMDSC) strongly suppress CD4 + T‐cell proliferation while the suppressive effect on CD8 + T cells is less pronounced. Splenic monocytic MDSCs (moMDSC) have a lower suppressive capacity, compared to grMDSC, on both CD4 + and CD8 + 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 2 − 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 + MDSCs are more suppressive than CD80 − MDSCs. Coculture of T reg and MDSCs leads to a stronger suppression of CD8 + T‐cell proliferation compared to the suppression observed by T reg 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.