Expression of indoleamine 2,3-dioxygenase in leukemic cells indicates an unfavorable prognosis in acute myeloid leukemia patients with intermediate-risk cytogenetics

Fukuno, Kenji; Hara, Takeshi; Tsurumi, Hisashi; Shibata, Yuhei; Mabuchi, Ryoko; Nakamura, Nobuhiko; Kitagawa, Junichi; Shimizu, Masahito; Ito, Hiroyasu; Moriwaki, Hisataka

doi:10.3109/10428194.2014.953150

Cited by 37 publications

(42 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This would suggest that in vivo MDSCs cells account for most IDO1 expression in LyP. Our findings on these cell lines agree with gene expression profiling data 27 (see Table S3 of ref. 26 for more details), where IDO1 was not ranked among the top 400 differentially expressed genes.…”

Section: Discussionsupporting

confidence: 90%

“…We report, for the first time, that several cell types other than malignant cells contribute to the expression of IDO1 in CTCL. Among hematologic malignancies, IDO1 expression has been previously found in the acute myeloid leukemia (AML) blasts 26 and in MDSCs in chronic lymphocytic leukemia (CLL) of B-cell origin 10 . We found the spectrum of IDO1-expressing cells to differ markedly among CTCL subtypes.…”

Section: Discussionmentioning

confidence: 74%

See 1 more Smart Citation

Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas

et al. 2017

View full text Add to dashboard Cite

Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography–tandem mass spectrometry (LC–MS/MS). Three CTCL cell lines also were studied. Expression of both IDO1 and TDO was upregulated in CTCL. In MF specimens and in the MF cell line MyLa2000, IDO1 expression exceeded that of TDO, whereas the opposite was true for LyP, ALCL, and corresponding Mac1/2A cell lines. The spectrum of IDO1-expressing cell types differed among CTCL subtypes and was reflected in the clinical behavior. In MF, SPTCL, and LyP, IDO1 was expressed by malignant cells and by CD33+ myeloid-derived suppressor cells, whereas in SPTCL CD163+ tumor-associated macrophages also expressed IDO1. Significantly elevated serum KYN/Trp ratios were found in patients with advanced stages of MF. Epacadostat, an IDO1 inhibitor, induced a clear decrease in KYN concentration in cell culture. These results show the importance of IDO1/TDO-induced immunosuppression in CTCL and emphasize its role as a new therapeutic target.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 74%

Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas

et al. 2017

View full text Add to dashboard Cite

show abstract

“…70) as well as IDO1 (REF. 71). In a separate study, the leukaemic cells from 12 of 15 patients with AML were found to suppress T cell proliferation in vitro by secreting arginase II, an enzyme that actively converts arginine into urea.…”

Section: Neoantigens and The Immune Responsementioning

confidence: 99%

Targeting neoantigens to augment antitumour immunity

et al. 2017

View full text Add to dashboard Cite

The past decade of cancer research has been marked by a growing appreciation of the role of immunity in cancer. Mutations in the tumour genome can cause tumours to express mutant proteins that are tumour specific and not expressed on normal cells (neoantigens). These neoantigens are an attractive immune target because their selective expression on tumours may minimize immune tolerance as well as the risk of autoimmunity. In this Review we discuss the emerging evidence that neoantigens are recognized by the immune system and can be targeted to increase antitumour immunity. We also provide a framework for personalized cancer immunotherapy through the identification and selective targeting of individual tumour neoantigens, and present the potential benefits and obstacles to this approach of targeted immunotherapy.

show abstract

“…IDO is also produced by cancer cells; therefore, Trp metabolism helps tumors evade the host immune responses and provides survival advantages to tumors [11]. Many studies have shown that a high level of IDO expression in tumors is a poor prognostic factor [13,14], and it is thought that IDO expression induces Trp deficiency in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy

Ninomiya

Nakamura

et al. 2020

Nutrients

Self Cite

View full text Add to dashboard Cite

Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship between skeletal muscles and low levels of tryptophan. A positive correlation was observed between the volume of skeletal muscles and serum tryptophan levels in patients with diffuse large B-cell lymphoma. Low levels of tryptophan reduced C2C12 myoblast cell proliferation and differentiation. Fiber diameters in the tibialis anterior of C57BL/6 mice fed a tryptophan-deficient diet were smaller than those in mice fed a standard diet. Metabolomics analysis revealed that tryptophan-deficient diet downregulated glycolysis in the gastrocnemius and upregulated the concentrations of amino acids associated with the tricarboxylic acid cycle. The weights and muscle fiber diameters of mice fed the tryptophan-deficient diet recovered after switching to the standard diet. Our data showed a critical role for tryptophan in regulating skeletal muscle mass. Thus, the tryptophan metabolism pathway may be a promising target for preventing or treating skeletal muscle atrophies.

show abstract

Expression of indoleamine 2,3-dioxygenase in leukemic cells indicates an unfavorable prognosis in acute myeloid leukemia patients with intermediate-risk cytogenetics

Cited by 37 publications

References 37 publications

Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas

Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas

Targeting neoantigens to augment antitumour immunity

Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy

Contact Info

Product

Resources

About