Immunosuppressive activities of adenosine in cancer

被引:223
作者
Allard, Bertrand [1 ,2 ]
Beavis, Paul A. [3 ,4 ]
Darcy, Phillip K. [3 ,5 ]
Stagg, John [1 ,2 ]
机构
[1] CRCHUM, Inst Canc Montreal, 900 Rue St Denis, Montreal, PQ H2X0A9, Canada
[2] Univ Montreal, Fac Pharm, Pavillon Jean Coutu,2940 Chemin Polytech, Montreal, PQ, Canada
[3] Peter MacCallum Canc Ctr, Canc Immunol Program, East Melbourne, Vic, Australia
[4] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia
[5] Univ Melbourne, Dept Pathol, Parkville, Vic, Australia
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词
REGULATORY T-CELLS; NEGATIVE BREAST-CANCER; MOUSE MELANOMA MODEL; NATURAL-KILLER-CELLS; EXTRACELLULAR ADENOSINE; A(2A) RECEPTOR; TUMOR-GROWTH; ECTONUCLEOTIDASE EXPRESSION; HIF-1-DEPENDENT REPRESSION; CD11B(+)GR1(+) CELLS;
D O I
10.1016/j.coph.2016.04.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Multiple immunosuppressive mechanisms impede anti-tumor immunity. Among them, the accumulation of extracellular adenosine is a potent and widespread strategy exploited by tumors to escape immunosurveillance through the activation of purinergic receptors. In the immune system, engagement of A2a and A2b adenosine receptors is a critical regulatory mechanism that protects tissues against excessive immune reactions. In tumors, this pathway is hijacked and hinders antitumor immunity, promoting cancer progression. Different groups have highlighted the therapeutic potential of blocking CD73-dependent adenosine-mediated immunosuppression to reinstate anti-tumor immunity. Phase clinical trials evaluating anti-CD73 antibodies and A2a receptor antagonists in cancer patients are currently ongoing. We here review the recent literature on the immunosuppressive effects of extracellular adenosine and discuss the development of adenosine inhibitors.
引用
收藏
页码:7 / 16
页数:10
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