MicroRNA-155 Is Required for Effector CD8+ T Cell Responses to Virus Infection and Cancer

被引:273
作者
Dudda, Jan C. [1 ]
Salaun, Bruno [1 ]
Ji, Yun [2 ]
Palmer, Douglas C. [2 ]
Monnot, Gwennaelle C. [1 ]
Merck, Estelle [1 ]
Boudousquie, Caroline [1 ]
Utzschneider, Daniel T. [4 ]
Escobar, Thelma M. [3 ]
Perret, Rachel [1 ]
Muljo, Stefan A. [3 ]
Hebeisen, Michael [1 ,5 ]
Rufer, Nathalie [1 ,5 ]
Zehn, Dietmar [4 ]
Donda, Alena [1 ]
Restifo, Nicholas P. [2 ]
Held, Werner [1 ]
Gattinoni, Luca [2 ]
Romero, Pedro [1 ]
机构
[1] Univ Lausanne, Ludwig Ctr Canc Res, CH-1066 Epalinges, Switzerland
[2] NCI, Ctr Canc Res, Bethesda, MD 20892 USA
[3] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA
[4] Univ Lausanne Hosp, Swiss Vaccine Res Inst, CH-1011 Lausanne, Switzerland
[5] Univ Lausanne Hosp, Dept Res, CH-1011 Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
CHRONIC VIRAL-INFECTION; IMMUNE-SYSTEM; CYTOKINE SIGNALING-1; B-CELL; DIFFERENTIATION; EXPRESSION; ANTIGEN; MEMORY; PERSISTENCE; ACTIVATION;
D O I
10.1016/j.immuni.2012.12.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
MicroRNAs (miRNAs) regulate the function of several immune cells, but their role in promoting CD8(+) T cell immunity remains unknown. Here we report that miRNA-155 is required for CD8(+) T cell responses to both virus and cancer. In the absence of miRNA-155, accumulation of effector CD8(+) T cells was severely reduced during acute and chronic viral infections and control of virus replication was impaired. Similarly, Mir155(-/-) CD8(+) T cells were ineffective at controlling tumor growth, whereas miRNA-155 overexpression enhanced the antitumor response. miRNA-155 deficiency resulted in accumulation of suppressor of cytokine signaling-1 (SOCS-1) causing defective cytokine signaling through STAT5. Consistently, enforced expression of SOCS-1 in CD8(+) T cells phenocopied the miRNA-155 deficiency, whereas SOCS-1 silencing augmented tumor destruction. These findings identify miRNA-155 and its target SOCS-1 as key regulators of effector CD8(+) T cells that can be modulated to potentiate immunotherapies for infectious diseases and cancer.
引用
收藏
页码:742 / 753
页数:12
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