Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase
Abstract
T lymphocytes undergo proliferation arrest when exposed to tryptophan shortage, which can be provoked by indoleamine 2,3-dioxygenase (IDO), an enzyme that is expressed in placenta and catalyzes tryptophan degradation. Here we show that most human tumors constitutively express IDO. We also observed that expression of IDO by immunogenic mouse tumor cells prevents their rejection by preimmunized mice. This effect is accompanied by a lack of accumulation of specific T cells at the tumor site and can be partly reverted by systemic treatment of mice with an inhibitor of IDO, in the absence of noticeable toxicity. These results suggest that the efficacy of therapeutic vaccination of cancer patients might be improved by concomitant administration of an IDO inhibitor.
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NSCLC patients have increased tryptophan catabolism compared with the general population, leading to higher serum kynurenine, which is associated with advanced stage at diagnosis, poor prognosis and chemotherapy resistance.
“Compared with the general population, patients with NSCLC have increased tryptophan catabolism, which leads to higher kynurenine serum concentrations and has been associated with advanced stage disease at diagnosis, an unfavourable prognosis and resistance to chemotherapy148,149.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [148]
IDO is considered an immune checkpoint in peripheral tolerance because tryptophan absence inhibits T cell proliferation and T cell apoptosis contributes to immunosuppression.
“Therefore, IDO is viewed as an immune checkpoint involved in peripheral immune tolerance owing to the fact that, in the absence of tryptophan, T cell proliferation is inhibited and T cell apoptosis contributes to immunosuppression148.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [148]
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- Authors
- Uyttenhove, C., Pilotte, L., Théate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., & Van den Eynde, B. J.
- Affiliations
- Ludwig Cancer Research (BE)
- Venue
- Nature Medicine
- Published
- 2003-09-21
- Volume
- 9
- Issue
- 10
- Pages
- 1269-1274
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1973251492
- Cited by
- 2,305
- References
- 39
- Citations by year
- 2026: 50 · 2025: 59 · 2024: 94 · 2023: 106 · 2022: 101 · 2021: 121 · 2020: 164 · 2019: 136 · 2018: 152 · 2017: 143 · 2016: 120 · 2015: 122 · 2014: 108 · 2013: 96 · 2012: 102
- FWCI
- 23.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- indoleamine 2,3-dioxygenase, tryptophan degradation, tumor immune resistance, tumor rejection, IDO inhibitors, cancer immunotherapy, therapeutic vaccination, tumor-specific T cells
- MeSH terms
- Animals, Female, Humans, Neoplasm Transplantation, Neoplasms, Placenta, Pregnancy, RNA, Messenger, Tryptophan, Tryptophan Oxygenase, CD8-Positive T-Lymphocytes, Tumor Escape, Cell Line, Tumor, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice
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