Inhibitors against thep110 delta isoform of phosphoinositide-3-OH kinase (PI(3) K) have shown remarkable therapeutic efficacy in some human leukaemias(1,2). As p110 delta is primarily expressed in leukocytes(3), drugs against p110 delta have not been considered for the treatment of solid tumours(4). Here we report that p110 delta inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110 delta inactivation in regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour regression. Thus, p110 delta inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.