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

SummaryMicroRNAs (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.

► TCR affinity regulates miRNA-155 expression crucial for CD8+ T cell accumulation.
► CD8 T cell survival and virus control in chronic infection depend on miRNA-155.
► miRNA-155 enhances CD8+ T cell cytokine signaling via targeting of SOCS-1.
► miRNA-155 and SOCS-1 modulation in specific CD8 T cells enhance their tumor control