title: Spontaneous cytotoxic T-Cell reactivity against indoleamine 2,3-dioxygenase-2.
abstract: 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.
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Rikke Bæk
authors.initials: RB
authors.lastname: Sørensen
authors.forename: Tania
authors.initials: T
authors.lastname: Køllgaard
authors.forename: Rikke Sick
authors.initials: RS
authors.lastname: Andersen
authors.forename: Joost Huibert
authors.initials: JH
authors.lastname: van den Berg
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
authors.forename: Per thor
authors.initials: Pt
authors.lastname: Straten
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
mesh_terms: D000595:Amino Acid Sequence; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D045325:HCT116 Cells; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020014:K562 Cells; D007680:Kidney Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D015789:HLA-A2 Antigen; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010455:Peptides