MicroRNAs are a class of small RNAs that are increasingly being recognized as important regulators of gene expression. Although hundreds of microRNAs are present in the mammalian genome, genetic studies addressing their physiological roles are at an early stage. We have shown that mice deficient for bic/microRNA-155 are immunodeficient and display increased lung airway remodeling. We demonstrate a requirement of bic/microRNA-155 for the function of B and T lymphocytes and dendritic cells. Transcriptome analysis of bic/microRNA-155 –deficient CD4 ⁺ T cells identified a wide spectrum of microRNA-155–regulated genes, including cytokines, chemokines, and transcription factors. Our work suggests that bic/microRNA-155 plays a key role in the homeostasis and function of the immune system.

The kinase PI(3)Kδ is shown to be required for the immunosuppressive function of regulatory T cells; inactivation of PI(3)Kδ in these cells leads to enhanced cytotoxic T-cell function and restricts tumour growth and metastasis in a variety of mouse tumour models. This paper shows that the p110δ isoform of phosphoinositide-3-OH kinase (PI(3)K) is critically required for the immunosuppressive function of regulatory T (Treg) cells. Inactivation of p110δ in Treg cells leads to enhanced cytotoxic T-cell function and restricts tumour growth and metastasis in a variety of mouse tumour models. This finding identifies p110δ as a druggable kinase target for which inhibition boosts the cancer-suppressive potential of the immune system. Inhibitors against the p110δ isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias1,2. As p110δ is primarily expressed in leukocytes3, drugs against p110δ have not been considered for the treatment of solid tumours4. Here we report that p110δ inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110δ inactivation in regulatory T cells unleashes CD8+ cytotoxic T cells and induces tumour regression. Thus, p110δ inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.