ArticlePloS one2012
Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 50 citations in OpenAlex.
- Translational investigations in the HN1901 phase II window-of-opportunity study investigating the biological activity of an IDO1 (IO102) and PD-L1 (IO103) immune-modulatory peptide cancer vaccines in squamous cell carcinoma of the head and neck.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Trial
- Pre-existing TGF-β-specific T-cell immunity in patients with pancreatic cancer predicts survival after checkpoint inhibitors combined with radiotherapy.Journal for immunotherapy of cancer · 2023Trial
- A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma.Nature medicine · 2021Trial
- Advances in Immunotherapy for Intrahepatic Cholangiocarcinoma.International journal of molecular sciences · 2026Review
- Immune modulatory vaccines targeting tumor microenvironment antigens: recent advances in oncology and beyond.Signal transduction and targeted therapy · 2026Review
- Proviruses in CD4Science translational medicine · 2025Article
- Impact of Indoleamine 2,3-Dioxygenase Enzyme Activity in Neuroendocrine Tumors.Neuroendocrinology · 2025Article
- Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab.Journal for immunotherapy of cancer · 2023Article
- IDO1 Protein Is Expressed in Diagnostic Biopsies from Both Follicular and Transformed Follicular Patients.International journal of molecular sciences · 2023Article
- Tumor microenvironment antigens.Seminars in immunopathology · 2023Review
- The immunosuppressive role of indoleamine 2, 3-dioxygenase in glioblastoma: mechanism of action and immunotherapeutic strategies.Medical oncology (Northwood, London, England) · 2022Review
- IDO Vaccine Ablates Immune-Suppressive Myeloid Populations and Enhances Antitumor Effects Independent of Tumor Cell IDO Status.Cancer immunology research · 2022Article
- Peptide vaccination activating Galectin-3-specific T cells offers a novel means to target Galectin-3-expressing cells in the tumor microenvironment.Oncoimmunology · 2022Article
- CCL22-based peptide vaccines induce anti-cancer immunity by modulating tumor microenvironment.Oncoimmunology · 2022Article
- The Kynurenine Pathway-New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies.International journal of molecular sciences · 2021Review
- Therapeutic Cancer Vaccination With a Peptide Derived From the Calreticulin Exon 9 Mutations Induces Strong Cellular Immune Responses in Patients WithFrontiers in oncology · 2021Article
- Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms.Cancers · 2020Review
- Telomerase and CD4 T Cell Immunity in Cancer.Cancers · 2020Review
- The metabolic enzyme arginase-2 is a potential target for novel immune modulatory vaccines.Oncoimmunology · 2020Article
- Anti-regulatory T cells are natural regulatory effector T cells.Cell stress · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides. METHODS AND
findingsIn the present study, we show that CD4(+) helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4(+) T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4(+) T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4(+) T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4(+) T cells and CD8(+) CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4(+) T cells.
conclusionIDO is spontaneously recognized by HLA class II-restricted, CD4(+) T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4(+) responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.