title: The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase.
abstract: Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in many settings including cancer. In recent years, we have described spontaneous CD8(+) as well as CD4(+) T-cell reactivity against IDO in the tumor microenvironment of different cancer patients as well as in the peripheral blood of both cancer patients and to a lesser extent in healthy donors. We have demonstrated that IDO-reactive CD8(+) T cells were peptide-specific, cytotoxic effector cells, which are able to recognize and kill IDO-expressing cells including tumor cells as well as dendritic cells. Consequently, IDO may serve as a widely applicable target for immunotherapeutic strategies with a completely different function as well as expression pattern compared to previously described antigens. IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, and IDO-based immunotherapy may consequently be synergistic with additional immunotherapy. In this regard, we have shown that the presence of IDO-specific T cells boosted immunity against CMV and tumor antigens by eliminating IDO(+) suppressive cells and changing the regulatory microenvironment. The current review summarizes current knowledge of IDO as a T-cell antigen, reports the initial results that are suggesting a general function of IDO-specific T cells in immunoregulation, and discusses future opportunities.
authors.affiliation: Department of Hematology, Center for Cancer Immune Therapy, Copenhagen University Hospital Herlev, Herlev Ringvej 75, Herlev, Denmark. mads.hald.andersen@regionh.dk
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003226:Congresses as Topic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology*; D009369:Neoplasms / Q000201:enzymology* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase