Cited by 877Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyCancer Immunotherapy and Biomarkers

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Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes

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Munn, David H., Sharma, Madhav D., Hou, Deyan, Baban, Babak, Lee, Jeffrey R., Antonia, Scott J., Messina, Jane L., Chandler, Phillip, Koni, Pandelakis A., Mellor, Andrew L.·2004·Journal of Clinical Investigation

DOI 10.1172/jci21583

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Abstract

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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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: Munn, David H.
Sharma, Madhav D.
Baban, Babak
Antonia, Scott J.
Messina, Jane L.
Koni, Pandelakis A.
Mellor, Andrew L.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2004-07-15
Volume: 114
Issue: 2
Pages: 280-290
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci21583
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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Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes

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