Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity.
Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity.
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DOI：
10.1016/j.celrep.2012.10.025
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发表时间：
2012-12-27
期刊：
影响因子：
8.8
通讯作者：
O'Connell RM
中科院分区：
文献类型：
--
作者：
Huffaker TB;Hu R;Runtsch MC;Bake E;Chen X;Zhao J;Round JL;Baltimore D;O'Connell RM
增加对抗肿瘤免疫的了解对于改善针对人类癌症的细胞免疫疗法是必要的。在这里，我们研究了两种免疫系统表达的microRNAs（miRNAs），miR-155和miR-146 a，在调节抗肿瘤免疫反应中的作用。我们的结果表明，miR-155促进和miR-146 a抑制T细胞的IFNγ应答，并减少体内实体瘤生长。使用一种新的miR-155和miR-146 a缺陷的双敲除（DKO）小鼠品系，我们还鉴定了这两种miRNA之间的上位关系。DKO小鼠具有与miR-155−/−小鼠相似的缺陷性T细胞应答和肿瘤生长表型。对T细胞区室的进一步分析显示，miR-155通过涉及Ship 1抑制的机制调节IFNγ表达。我们的工作揭示了miRNA在CD 4+和CD 8 + T细胞介导的抗肿瘤免疫的相互调节中的关键作用，并证明了miR-155在促进免疫应答过程中的主导作用。
An increased understanding of antitumor immunity is necessary to improve cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs), miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits IFNγ responses by T cells and reduced solid tumor growth in vivo. Using a novel double knockout (DKO) mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155−/− mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4+ and CD8+ T cell-mediated antitumor immunity, and demonstrates the dominant nature of miR-155 during its promotion of immune responses.
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影响因子：
4.4
作者：
Oertli, Mathias;Engler, Daniela B.;Mueller, Anne
通讯作者：
Mueller, Anne
影响因子：
32.4
作者：
O'Connell RM;Kahn D;Gibson WS;Round JL;Scholz RL;Chaudhuri AA;Kahn ME;Rao DS;Baltimore D
通讯作者：
Baltimore D
使用miRNA Mimetics在体内重新编程与肿瘤相关的树突状细胞触发了针对卵巢癌的保护性免疫。
影响因子：
11.2
作者：
Cubillos-Ruiz JR;Baird JR;Tesone AJ;Rutkowski MR;Scarlett UK;Camposeco-Jacobs AL;Anadon-Arnillas J;Harwood NM;Korc M;Fiering SN;Sempere LF;Conejo-Garcia JR
通讯作者：
Conejo-Garcia JR
DOI：
10.1126/science.1139253
发表时间：
2007-04-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rodriguez A;Vigorito E;Clare S;Warren MV;Couttet P;Soond DR;van Dongen S;Grocock RJ;Das PP;Miska EA;Vetrie D;Okkenhaug K;Enright AJ;Dougan G;Turner M;Bradley A
通讯作者：
Bradley A
影响因子：
20.3
作者：
Jiang, Shan;Li, Chaoran;Li, Qi-Jing
通讯作者：
Li, Qi-Jing