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

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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.
Original languageEnglish
JournalCancer Research
Volume71
Issue number6
Pages (from-to)2038-44
Number of pages7
ISSN0008-5472
DOIs
Publication statusPublished - 15 Mar 2011

    Research areas

  • Amino Acid Sequence, Carcinoma, Renal Cell, Cell Line, Tumor, Cells, Cultured, Cytotoxicity, Immunologic, Flow Cytometry, HCT116 Cells, HLA-A2 Antigen, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, K562 Cells, Kidney Neoplasms, Melanoma, Neoplasms, Peptides, Protein Binding, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Cytotoxic

ID: 32761603