1. MicroRNA-155 and its target SOCS-1 shape the effector CD8+ T cell response to virus and cancer
- Author
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Dudda Jan C, Salaun B, Ji Yun, Palmer Douglas C, Monnot Gwennaelle C, Merck Estelle, Boudousquie Caroline, Utzschneider Daniel T, Escobar Thelma M, Perret Rachel, Muljo Stefan A, Hebeisen M, Rufer Nathalie, Zehn Dietmar, Donda Alena, Restifo Nicholas P, Held Werner, Gattinoni Luca, and Romero Pedro
- Abstract
MicroRNAs regulate the function of several immune cells but their role in promoting CD8+ T cell immunity remains unknown. Here we report that miR 155 is required for CD8+ T cell responses to both virus and cancer. In the absence of miR 155 accumulation of effector CD8+ T cells was severely reduced during acute and chronic viral infections and control of virus levels was impaired. Similarly miR 155 deficient CD8+ T cells were poorly effective at controlling tumor growth while miR 155 overexpression enhanced the antitumor response. miR 155 deficiency caused accumulation of SOCS 1 resulting in defective cytokine signaling through STAT5. Consistently enforced expression of SOCS 1 in CD8+ T cells phenocopied miR 155 deficiency whereas SOCS 1 silencing augmented tumor destruction. These findings identify miR 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.
- Published
- 2013