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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-06-11

AUTHORS

Khaled Ali, Dalya R Soond, Roberto Pineiro, Thorsten Hagemann, Wayne Pearce, Ee Lyn Lim, Hicham Bouabe, Cheryl L Scudamore, Timothy Hancox, Heather Maecker, Lori Friedman, Martin Turner, Klaus Okkenhaug, Bart Vanhaesebroeck

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. More... »

PAGES

407-411

References to SciGraph publications

  • 2014-01-31. PI3K and cancer: lessons, challenges and opportunities in NATURE REVIEWS DRUG DISCOVERY
  • 2012-09-21. Paths to stemness: building the ultimate antitumour T cell in NATURE REVIEWS CANCER
  • 2012-03-22. Coordinated regulation of myeloid cells by tumours in NATURE REVIEWS IMMUNOLOGY
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    http://scigraph.springernature.com/pub.10.1038/nature13444

    DOI

    http://dx.doi.org/10.1038/nature13444

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1027340229

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24919154


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