title: MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer.
abstract: 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.
authors.affiliation: Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Dudda
authors.forename: Bruno
authors.initials: B
authors.lastname: Salaun
authors.forename: Yun
authors.initials: Y
authors.lastname: Ji
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Palmer
authors.forename: Gwennaelle C
authors.initials: GC
authors.lastname: Monnot
authors.forename: Estelle
authors.initials: E
authors.lastname: Merck
authors.forename: Caroline
authors.initials: C
authors.lastname: Boudousquie
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Utzschneider
authors.forename: Thelma M
authors.initials: TM
authors.lastname: Escobar
authors.forename: Rachel
authors.initials: R
authors.lastname: Perret
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Muljo
authors.forename: Michael
authors.initials: M
authors.lastname: Hebeisen
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.forename: Alena
authors.initials: A
authors.lastname: Donda
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Werner
authors.initials: W
authors.lastname: Held
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006801:Humans; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
chemical_list: D016207:Cytokines; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D034741:RNA, Small Interfering; D050800:STAT6 Transcription Factor; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins