Publication Date:
2014-06-12
Description:
Inhibitors against the p110delta isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110delta is primarily expressed in leukocytes, drugs against p110delta have not been considered for the treatment of solid tumours. Here we report that p110delta inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110delta inactivation in regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour regression. Thus, p110delta inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501086/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ali, Khaled -- Soond, Dalya R -- Pineiro, Roberto -- Hagemann, Thorsten -- Pearce, Wayne -- Lim, Ee Lyn -- Bouabe, Hicham -- Scudamore, Cheryl L -- Hancox, Timothy -- Maecker, Heather -- Friedman, Lori -- Turner, Martin -- Okkenhaug, Klaus -- Vanhaesebroeck, Bart -- 095691/Wellcome Trust/United Kingdom -- 095691/Z/11/Z/Wellcome Trust/United Kingdom -- 12888/Cancer Research UK/United Kingdom -- 14355/Cancer Research UK/United Kingdom -- A10200/Cancer Research UK/United Kingdom -- A12888/Cancer Research UK/United Kingdom -- A15965/Cancer Research UK/United Kingdom -- BB/E009867/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- C18270/A12888/Cancer Research UK/United Kingdom -- C23338/A10200/Cancer Research UK/United Kingdom -- C23338/A15965/Cancer Research UK/United Kingdom -- England -- Nature. 2014 Jun 19;510(7505):407-11. doi: 10.1038/nature13444. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK [2]. ; 1] Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK [2] [3]. ; Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. ; UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK. ; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK. ; Mary Lyon Centre, MRC Harwell, Harwell Science and Innovation Campus, Harwell OX11 0RD, UK. ; Piramed Pharma, 957 Buckingham Avenue, Slough, Berkshire SL1 4NL, UK. ; Cancer Signaling and Translational Oncology, Genentech Inc, 1 DNA Way, South San Francisco, California 94080-4990, USA. ; 1] Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919154" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antineoplastic Agents/pharmacology
;
Enzyme Activation/drug effects
;
Enzyme Inhibitors/*pharmacology
;
Immune Tolerance/*drug effects/immunology
;
Mice
;
Neoplasms/*enzymology/*immunology
;
Phosphatidylinositol 3-Kinases/*metabolism
;
T-Lymphocytes, Regulatory/*drug effects/enzymology/immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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