MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Apoptosis / genetics
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / genetics
  • Humans
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic choriomeningitis virus / physiology*
  • Melanoma, Experimental / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Small Interfering / genetics
  • STAT6 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Virus Replication / genetics


  • Cytokines
  • MIRN155 microRNA, human
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • RNA, Small Interfering
  • STAT6 Transcription Factor
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins