Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.
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Peer-reviewed
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Abstract
Inhibitors against the p110δ isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumours. 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.
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Keywords
Animals, Antineoplastic Agents, Enzyme Activation, Enzyme Inhibitors, Immune Tolerance, Mice, Neoplasms, Phosphatidylinositol 3-Kinases, T-Lymphocytes, Regulatory
Journal Title
Nature
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Journal ISSN
0028-0836
1476-4687
1476-4687
Volume Title
510
Publisher
Springer Science and Business Media LLC