Department of Immunology-Physiology, Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Jette, Belgium.
Int J Cancer. 2014 Mar 1;134(5):1077-90. doi: 10.1002/ijc.28449. Epub 2013 Sep 23.
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 (Treg ) 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 NO2 (-) 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 Treg and MDSCs leads to a stronger suppression of CD8(+) T-cell proliferation compared to the suppression observed by Treg 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.
虽然髓系来源的抑制细胞（MDSCs）的主要作用部位很可能是肿瘤微环境，但迄今为止，对这些细胞的研究主要局限于脾脏来源的 MDSCs。在这项研究中，我们比较了不同皮下小鼠肿瘤模型中脾脏和肿瘤来源的 MDSC 的抑制能力。我们研究了涉及哪些抑制机制。最后，我们研究了 MDSC 和调节性 T 细胞（Treg）是否在抑制 T 细胞反应中合作。在所有模型中，脾脏粒细胞 MDSC（grMDSC）强烈抑制 CD4+T 细胞增殖，而对 CD8+T 细胞的抑制作用则不那么明显。与 grMDSC 相比，脾脏单核细胞 MDSC（moMDSC）对 CD4+和 CD8+T 细胞增殖的抑制能力较低。与肿瘤来源的 MDSC 相比，源自肿瘤的 grMDSC 和 moMDSC 具有更强的抑制活性，与肿瘤来源的 moMDSC 产生更高的 NO2（-）和两种亚群的精氨酸酶活性相关。与外周对应物相比，源自肿瘤的 grMDSC 上 CD80 的表达也升高。与肿瘤细胞的直接接触是上调 CD80 所必需的，并且 CD80+MDSC 比 CD80-MDSC 更具抑制作用。Treg 和 MDSC 的共培养导致 CD8+T 细胞增殖的抑制比单独观察到的 Treg 或 MDSC 更强。因此，我们表明，肿瘤浸润的 MDSC 具有比其外周对应物更强的抑制能力，并且各种抑制机制解释了这种差异。
