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: Rikke Bæk Sørensen, Tania Køllgaard, Rikke Sick Andersen, Joost Huibert van den Berg, Inge Marie Svane, Per thor Straten, Mads Hald Andersen
• Journal: Cancer research (Cancer Res) Vol. 71 Issue 6 Pg. 2038-44 (Mar 15 2011) ISSN: 1538-7445 [Electronic] United States
• PMID: 21406395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2011 AACR

Chemical References

• HLA-A2 Antigen
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Peptides

Topics

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