Spontaneous Cytotoxic T-Cell Reactivity against Indoleamine 2,3-Dioxygenase-2

被引:47
作者
Sorensen, Rikke Baek [1 ]
Kollgaard, Tania [1 ]
Andersen, Rikke Sick [1 ]
van den Berg, Joost Huibert [1 ]
Svane, Inge Marie [1 ]
Straten, Per Thor [1 ]
Andersen, Mads Hald [1 ]
机构
[1] Copenhagen Univ Hosp, Dept Hematol, Ctr Canc Immune Therapy, Herlev, Denmark
基金
英国医学研究理事会;
关键词
CANCER; INHIBITION; TARGET; SUPPRESSION; IDO2;
D O I
10.1158/0008-5472.CAN-10-3403
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Several lines of data have suggested a possible link between the indoleamine 2,3-dioxygenase (IDO)-like protein IDO2 and cancer. First, IDO2 expression has been described in human tumors, including renal, gastric, colon, and pancreatic tumors. Second, the apparent selective inhibition of IDO2 by the D stereoisomer of the IDO blocker 1-methyl-tryptophan (1MT), which tends to be more active than the L-isomer in a variety of biological assays for IDO function, suggests that IDO2 may be important to sustain immune escape and growth of tumors. Especially, D-1MT heightens chemotherapeutic efficacy in mouse models of cancer in a nontoxic fashion. Here, we describe the immunogenicity of IDO2 by showing the presence of spontaneous cytotoxic T-cell reactivity against IDO2 in peripheral blood of both healthy donors and cancer patients. Furthermore, we show that these IDO2-specific T cells are cytotoxic effector cells that recognize and kill tumor cells. Our data suggest that IDO2 might be a useful target for anticancer immunotherapeutic strategies. Cancer Res; 71(6); 2038-44. (C) 2011 AACR.
引用
收藏
页码:2038 / 2044
页数:7
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