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

被引：422

作者：

Ali, Khaled ^{[1
]}

Soond, Dalya R. ^{[2
]}

Pineiro, Roberto ^{[1
]}

Hagemann, Thorsten ^{[3
]}

Pearce, Wayne ^{[1
]}

Lim, Ee Lyn ^{[2
]}

Bouabe, Hicham ^{[2
]}

Scudamore, Cheryl L. ^{[4
]}

Hancox, Timothy ^{[5
]}

Maecker, Heather ^{[6
]}

Friedman, Lori ^{[6
]}

Turner, Martin ^{[2
]}

Okkenhaug, Klaus ^{[2
]}

Vanhaesebroeck, Bart ^{[1
]}

机构：

[1] UCL, UCL Canc Inst, London WC1E 6DD, England

[2] Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge CB22 3AT, England

[3] Queen Mary Univ London, Barts Canc Inst, Ctr Canc & Inflammat, London EC1M 6BQ, England

[4] MRC Harwell, Mary Lyon Ctr, Harwell OX11 0RD, Berks, England

[5] Piramed Pharma, Slough SL1 4NL, Berks, England

[6] Genentech Inc, Canc Signaling & Translat Oncol, San Francisco, CA 94080 USA

来源：

NATURE | 2014年 / 510卷 / 7505期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

PHOSPHOINOSITIDE; 3-KINASE; SUPPRESSOR-CELLS; INFLAMMATION; IDELALISIB; INHIBITION; ISOFORM; DELTA; PI3K;

D O I：

10.1038/nature13444

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Inhibitors against thep110 delta isoform of phosphoinositide-3-OH kinase (PI(3) K) have shown remarkable therapeutic efficacy in some human leukaemias(1,2). As p110 delta is primarily expressed in leukocytes(3), drugs against p110 delta have not been considered for the treatment of solid tumours(4). Here we report that p110 delta inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110 delta inactivation in regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour regression. Thus, p110 delta inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.

引用

页码：407 / +

页数：9

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