Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
Immunity. 2013 Apr 18;38(4):742-53. doi: 10.1016/j.immuni.2012.12.006.
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.
微小 RNA（miRNAs）调节多种免疫细胞的功能，但它们在促进 CD8(+)T 细胞免疫中的作用尚不清楚。在这里，我们报告 miRNA-155 是 CD8(+)T 细胞对病毒和癌症反应所必需的。在缺乏 miRNA-155 的情况下，效应性 CD8(+)T 细胞在急性和慢性病毒感染期间的积累严重减少，病毒复制的控制受到损害。同样，Mir155(-/-)CD8(+)T 细胞在控制肿瘤生长方面无效，而 miRNA-155 的过表达增强了抗肿瘤反应。miRNA-155 缺乏导致细胞因子信号转导抑制因子-1（SOCS-1）的积累，从而导致通过 STAT5 的细胞因子信号转导缺陷。一致地，SOCS-1 在 CD8(+)T 细胞中的强制表达可模拟 miRNA-155 的缺乏，而 SOCS-1 的沉默则增强了肿瘤的破坏。这些发现确定了 miRNA-155 和其靶基因 SOCS-1 是效应性 CD8(+)T 细胞的关键调节因子，可以通过调节它们来增强针对传染病和癌症的免疫疗法。
