Spontaneous cytotoxic T-Cell reactivity against indoleamine 2,3-dioxygenase-2

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Rikke Bæk Sørensen, Tania Køllgaard, Rikke Sick Andersen, Joost Huibert van den Berg, Inge Marie Svane, Per thor Straten, Mads Hald Andersen

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.
TidsskriftCancer Research
Udgave nummer6
Sider (fra-til)2038-44
Antal sider7
StatusUdgivet - 15 mar. 2011

ID: 40197095