The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index.
Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes
Open accessAbstract
One mechanism contributing to immunologic unresponsiveness toward tumors may be presentation of tumor antigens by tolerogenic host APCs.We show that mouse tumor-draining LNs (TDLNs) contained a subset of plasmacytoid DCs (pDCs) that constitutively expressed immunosuppressive levels of the enzyme indoleamine 2,3-dioxygenase (IDO).Despite comprising only 0.5% of LN cells, these pDCs in vitro potently suppressed T cell responses to antigens presented by the pDCs themselves and also, in a dominant fashion, suppressed T cell responses to third-party antigens presented by nonsuppressive APCs.Adoptive transfer of DCs from TDLNs into naive hosts created profound local T cell anergy, specifically toward antigens expressed by the transferred DCs.Anergy was prevented by targeted disruption of the IDO gene in the DCs or by administration of the IDO inhibitor drug 1-methyl-D-tryptophan to recipient mice.Within the population of pDCs, the majority of the functional IDO-mediated suppressor activity segregated with a novel subset of pDCs coexpressing the B-lineage marker CD19.We hypothesize that IDO-mediated suppression by pDCs in TDLNs creates a local microenvironment that is potently suppressive of host antitumor T cell responses.Nonstandard abbreviations used: indoleamine 2,3-dioxygenase (IDO); 1-methyl-D-tryptophan (1MT); mixed leukocyte reaction (MLR); plasmacytoid DC (pDC); regulatory T cell (Treg); T cell receptor (TCR); tumor-draining LN (TDLN). Conflict of interest:The authors have declared that no conflict of interest exists.
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“In preclinical models, heightened activity of the Trp-Kyn-AhR pathway has been linked to impairment of antitumor immunity and tumor growth (16,17).”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [16]
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Metadata
- Authors
- Munn, D. H., Sharma, M. D., Hou, D., Baban, B., Lee, J. R., Antonia, S. J., Messina, J. L., Chandler, P., Koni, P. A., & Mellor, A. L.
- Affiliations
- Augusta University (US)
- University of South Florida (US)
- Corresponding author
- Munn, David H.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2004-07-15
- Volume
- 114
- Issue
- 2
- Pages
- 280-290
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2143565660
- Cited by
- 852
- References
- 85
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 24 · 2023: 15 · 2022: 32 · 2021: 37 · 2020: 34 · 2019: 29 · 2018: 31 · 2017: 40 · 2016: 27 · 2015: 45 · 2014: 38 · 2013: 53 · 2012: 39
- FWCI
- 19.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Carlos and Marguerite Mason Trust
- National Institutes of Health
- National Cancer Institute (R01CA096651, R01 CA103220)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD041187)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- indoleamine 2,3-dioxygenase, plasmacytoid dendritic cells, tumor-draining lymph nodes, immunosuppression, T cell anergy, tumor antigen presentation, CD19, 1-methyl-D-tryptophan, antitumor immunity, regulatory T cells, mixed lymphocyte reaction
- MeSH terms
- Animals, Antigen-Presenting Cells, Dendritic Cells, Female, Humans, Immunosuppression Therapy, Lymph Nodes, Lymphocyte Activation, Mice, Inbred Strains, Neoplasms, Random Allocation, T-Lymphocytes, Tryptophan Oxygenase, Survival Rate, Mice, Knockout, Antigens, CD19, Adoptive Transfer, CD11c Antigen, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice
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