Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment.
Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment.
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单核细胞CCR2（+）髓样衍生的抑制细胞通过将活化的CD8 T细胞浸润限制在肿瘤微环境中，从而促进免疫逃逸。
DOI：
10.1158/0008-5472.can-11-1792
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发表时间：
2012-02-15
期刊：
影响因子：
11.2
通讯作者：
Wolchok JD
中科院分区：
文献类型：
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作者：
Lesokhin AM;Hohl TM;Kitano S;Cortez C;Hirschhorn-Cymerman D;Avogadri F;Rizzuto GA;Lazarus JJ;Pamer EG;Houghton AN;Merghoub T;Wolchok JD
髓源性抑制细胞（MDSC）是一群异质性细胞，在肿瘤形成过程中积聚，促进免疫逃逸并使肿瘤进展。MDSC是形成免疫抑制性肿瘤微环境的重要因素，该环境会阻断细胞毒性抗肿瘤T效应细胞的作用。这些细胞的异质性对研究单个MDSC亚型在体内的作用构成了重大障碍。在此，我们证明粒细胞 - 巨噬细胞集落刺激因子（GM - CSF），一种对MDSC群体的数量和功能发展至关重要的细胞因子，可促进以表达CD11b和趋化因子受体CCR2为特征的单核细胞源性MDSC群体的扩增。利用一种毒素介导的消融策略来靶向表达CCR2的细胞，我们表明这些单核细胞MDSC调节活化的CD8 T细胞进入肿瘤部位，从而限制了免疫疗法的疗效。我们的研究结果表明，对单核细胞MDSC进行治疗性靶向将提高免疫疗法的效果。
Myeloid derived suppressor cells (MDSC) are a heterogeneous population of cells that accumulate during tumor formation, facilitate immune escape and enable tumor progression. MDSC are important contributors to the development of an immunosuppressive tumor microenvironment that blocks the action of cytotoxic anti-tumor T effector cells. Heterogeneity in these cells poses a significant barrier to studying the in vivo contributions of individual MDSC subtypes. Herein, we demonstrate that granulocyte-macrophage colony stimulating factor (GM-CSF), a cytokine critical for the numeric and functional development of MDSC populations, promotes expansion of a monocyte-derived MDSC population characterized by expression of CD11b and the chemokine receptor CCR2. Utilizing a toxin mediated ablation strategy to target CCR2-expressing cells, we show that these monocytic MDSCs regulate entry of activated CD8 T cells into the tumor site, thereby limiting the efficacy of immunotherapy. Our results argue that therapeutic targeting of monocytic MDSCs would enhance outcomes in immunotherapy.