Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways.
Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways.
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DOI：
10.1016/j.immuni.2014.10.020
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发表时间：
2014-12-18
期刊：
影响因子：
32.4
通讯作者：
Murray, Peter J.
中科院分区：
文献类型：
--
作者：
Haverkamp, Jessica M.;Smith, Amber M.;Weinlich, Ricardo;Dillon, Christopher P.;Qualls, Joseph E.;Neale, Geoffrey;Koss, Brian;Kim, Young;Bronte, Vincenzo;Herold, Marco J.;Green, Douglas R.;Opferman, Joseph T.;Murray, Peter J.
非化解性炎症扩大了能够抑制T细胞功能的骨髓抑制细胞的异质群体。这种异质性混淆了单个骨髓亚群的功能解剖，并提出了抗肿瘤免疫和免疫治疗的障碍。通过对细胞死亡途径的基因操作，我们发现单核细胞抑制细胞亚群，而不是粒细胞亚群，需要持续的c-FLIP表达来防止依赖于caspase-8、不依赖于ripk3的细胞死亡。粒细胞亚群的发展需要mcl -1介导的内在线粒体死亡途径的控制。单核细胞抑制因子耐受MCL-1的缺失，提供细胞因子增加MCL-1相关蛋白A1的表达。单核细胞抑制因子介导T细胞抑制，而它们的粒细胞抑制因子缺乏抑制功能。通过条件MCL-1缺失造成的粒细胞亚群的缺失并没有改变肿瘤的发病率，这表明单核细胞是体内功能性免疫抑制亚群。因此，死亡通路的调节决定了骨髓抑制细胞的发育、存活和功能。
Non-resolving inflammation expands a heterogeneous population of myeloid suppressor cells capable of inhibiting T cell function. This heterogeneity has confounded the functional dissection of individual myeloid subpopulations and presents an obstacle for anti-tumor immunity and immunotherapy. Using genetic manipulation of cell death pathways, we found the monocytic suppressor cell subset, but not the granulocytic subset requires continuous c-FLIP expression to prevent caspase-8-dependent, RIPK3-independent cell death. Development of the granulocyte subset requires MCL-1-mediated control of the intrinsic mitochondrial death pathway. Monocytic suppressors tolerate the absence of MCL-1 provided cytokines increase expression of the MCL-1-related protein A1. Monocytic suppressors mediate T cell suppression, while their granulocytic counterparts lack suppressive function. The loss of the granulocytic subset via conditional MCL-1 deletion did not alter tumor incidence implicating the monocytic compartment as the functionally immunosuppressive subset in vivo. Thus, death pathway modulation defines the development, survival and function of myeloid suppressor cells.
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影响因子：
56.9
作者：
Opferman, JT;Iwasaki, H;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
8.8
作者：
Dillon CP;Oberst A;Weinlich R;Janke LJ;Kang TB;Ben-Moshe T;Mak TW;Wallach D;Green DR
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
20.3
作者：
Movahedi, Kiavash;Guilliams, Martin;Van Ginderachter, Jo A.
通讯作者：
Van Ginderachter, Jo A.
影响因子：
20.3
作者：
Huang, Qi-Quan;Perlman, Harris;Pope, Richard M.
通讯作者：
Pope, Richard M.