Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase

By C. Uyttenhove, L. Pilotte, I. Theate, V. Stroobant, D. Colau, Nicolas Parmentier, T. Boon, B. Eynde. Nature Medicine, 2003

2,301 citations recorded by the source corpus.

Subfields: Biological Psychiatry, Immunology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/d58c9b4823c861a527476064b0389683390d90b2

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In Biological Psychiatry

1. D. Munn
2. A. Mellor
3. W. Zou
4. Erika L. Pearce
5. F. Quintana

In Immunology

1. D. Munn
2. A. Mellor
3. Guido Kroemer
4. L. Zitvogel
5. W. Zou
6. D. Gabrilovich
7. Michael D. Buck
8. Erika L. Pearce

In Psychiatry and Mental health

1. D. Munn
2. A. Mellor
3. W. Zou
4. Gabriel A. Rabinovich

Citations in the corpus

• The Combined Effects of Tryptophan Starvation and Tryptophan Catabolites Down-Regulate T Cell Receptor ζ-Chain and Induce a Regulatory Phenotype in Naive T Cells1 (2006, background): “Discussion The immunosuppressive pathway of tryptophan catabolism has been implicated, with either protective or disease-promoting roles, in a variety of physiopathologic conditions, ranging from pregnancy (3) to transplantation (4), from autoimmunity (5) and inflammation (6, 7, 46) to neoplasia (11”
• Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. (2007, background): “Transfection of IDO into tumor cells protects them from immune-mediated rejection (5), while inhibiting IDO in tumor-bearing hosts allows conventional chemotherapy to disrupt tolerance toward established tumors and trigger anti-tumor immune responses (6, 7).”
• Regulation of the immune response by the aryl hydrocarbon receptor (2018, background): “Low Trp levels induce T cell cycle arrest and death (Uyttenhove et al., 2003).”
• Immunosuppressive strategies that are mediated by tumor cells. (2007, background): “The authors demonstrated that immunogenic tumors engineered to overexpress IDO grew more aggressively in immunocompetent hosts and this effect correlated with a decreased accumulation of activated T-cells at the tumor site (98).”
• Cancer despite immunosurveillance: immunoselection and immunosubversion (2006, background): “More importantly, tryptophan degradation by indoleamine 2,3-dioxygenase ( IDO ), which is constitutively expressed by human tumours (particularly by prostate, colon and pancreatic carcinomas, but also by interdigitating DCs), promotes resistance to immune-mediated rejection of the tumour cell”
• Molecular and genetic properties of tumors associated with local immune cytolytic activity (2015, positive): “23 (Data S6A) showed increased probability of amplification in low-CYT tumors (pan-cancer and breast) and is adjacent to IDO1 and IDO2, enzymes that degrade extracellular tryptophan and create a potent immunosuppressive microenvironment, which may explain the associated reduction in CYT (Uyttenhove ”
• Ido expression by dendritic cells: tolerance and tryptophan catabolism (2004, background): “As summarized in Table 1 , so far, physiological IDO activity has been implicated in T-cell tolerance to tumour”
• T cell metabolism drives immunity (2015, background): “IDO, which is often expressed at high levels by APCs or tumor cells, can deplete tryptophan within a tissue microenvironment, and this in turn can lead to inhibition of effector T cell proliferation and induction of anergy (Munn et al., 2002; Uyttenhove et al., 2003).”
• Up-Regulation of PD-L1, IDO, and Tregs in the Melanoma Tumor Microenvironment Is Driven by CD8+ T Cells (2013, background): “…in mouse models include extrinsic suppression of CD8 + effector cells by CD4 + CD25 + FoxP3 + regulatory T cells (T regs ) (6), metabolic deregulation via tryptophan catabolism by indoleamine-2,3-dioxygenase (IDO) (7), and engagement of the inhibitory receptor PD-1 by the ligand PD-L1/B7-H1 (8, 9).”
• Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2018, positive): “Inhibition of indoleamine 2,3-dioxygenase, which mediates the first step in the conversion of tryptophan in de novoNAD+ synthesis, shows promise in mice as an antitumor therapeutic target (Friberg et al., 2002; Muller et al., 2005; Uyttenhove et al., 2003).”
• Metabolic Instruction of Immunity (2017, neutral): “TAMs, MDSCs, and tolerizing dendritic cells (DCs) can suppress TILs through expression of essential amino acid (EAA)-degrading enzymes such as Arg1 and indoleamine-2,3dioxygenase (IDO) (Figure 1) (Lee et al., 2002; Munn et al., 2002; Rodriguez, 2004; Uyttenhove et al., 2003).”