TY - JOUR

T1 - Spontaneous cytotoxic T-Cell reactivity against indoleamine 2,3-dioxygenase-2

AU - Sørensen, Rikke Bæk

AU - Køllgaard, Tania

AU - Andersen, Rikke Sick

AU - van den Berg, Joost Huibert

AU - Svane, Inge Marie

AU - Straten, Per thor

AU - Andersen, Mads Hald

N1 - ©2011 AACR

PY - 2011/3/15

Y1 - 2011/3/15

N2 - 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.

AB - 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.

U2 - http://dx.doi.org/10.1158/0008-5472.CAN-10-3403

DO - http://dx.doi.org/10.1158/0008-5472.CAN-10-3403

M3 - Journal article

VL - 71

SP - 2038

EP - 2044

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 6

ER -