Inactivation of the PI3K p110δ breaks regulatory T cell-mediated immune tolerance to cancer

摘要

Inhibitors against the p110δ isoform of PI3K have shown remarkable therapeutic efficacy in some human leukaemias^,. Since p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumours. We report here 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 (Treg) 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.