2. Academic Validation
  3. Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer

Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer

  • Nature. 2014 Jun 19;510(7505):407-411. doi: 10.1038/nature13444.
Khaled Ali 1,  Dalya R Soond  # 2,  Roberto Pineiro  # 1,  Thorsten Hagemann 3,  Wayne Pearce 1,  Ee Lyn Lim 2,  Hicham Bouabe 2,  Cheryl L Scudamore 4,  Timothy Hancox 5,  Heather Maecker 6,  Lori Friedman 6,  Martin Turner 2,  Klaus Okkenhaug 2,  Bart Vanhaesebroeck 1
Affiliations

Affiliations

  • 1 UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK.
  • 2 Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • 3 Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
  • 4 Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, Hatfield, Hertfordshire AL9 7TA, UK.
  • 5 Piramed Pharma, 957 Buckingham Avenue, Slough, Berkshire, SL1 4NL, UK.
  • 6 Cancer Signaling and Translational Oncology, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080-4990, USA.
  • # Contributed equally.
PMID: 24919154 DOI: 10.1038/nature13444
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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