Mechanism of interferon-gamma action. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity.

Takikawa, Osamu; Kuroiwa, Takashi; Yamazaki, Fumio; Kido, Ryo

doi:10.1016/s0021-9258(19)77982-4

Cited by 429 publications

(96 citation statements)

References 47 publications

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“…There are two hypotheses that might explain this putative contradiction. First, local tryptophan depletion has been reported to decrease the proliferation of tumor cell lines in an in vitro model [ 16 , 17 ]. Second, the IFN-γ is a crucial cytokine to induce IDO1 expression [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…First, local tryptophan depletion has been reported to decrease the proliferation of tumor cell lines in an in vitro model [ 16 , 17 ]. Second, the IFN-γ is a crucial cytokine to induce IDO1 expression [ 17 ]. During an antitumor immune response, IFN-γ and other pro-inflammatory cytokines are secreted, and IDO1 expression could be a marker of an ongoing antitumoral immune response.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas

Donizy

Kopczyński

et al. 2021

IJMS

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The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas

Donizy

Kopczyński

et al. 2021

IJMS

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“…The mechanisms by which tryptophan restriction leads to suppression of in vitro viral replication have thus not been entirely straightforward. Tryptophan starvation stresses mammalian cells and inhibits their proliferation [46]. It is perhaps not surprising that such stress renders cells less efficient as hosts for viral replication, whether or not this is actually exploited as an antiviral defense mechanism in vivo.…”

Section: Discussionmentioning

confidence: 99%

Opposing Biological Functions of Tryptophan Catabolizing Enzymes During Intracellular Infection

Divanovic

Sawtell

Trompette

et al. 2011

The Journal of Infectious Diseases

104

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Recent studies have underscored physiological and pathophysiological roles for the tryptophan-degrading enzyme indolamine 2,3-dioxygenase (IDO) in immune counterregulation. However, IDO was first recognized as an antimicrobial effector, restricting tryptophan availability to Toxoplasma gondii and other pathogens in vitro. The biological relevance of these findings came under question when infectious phenotypes were not forthcoming in IDO-deficient mice. The recent discovery of an IDO homolog, IDO-2, suggested that the issue deserved reexamination. IDO inhibition during murine toxoplasmosis led to 100% mortality, with increased parasite burdens and no evident effects on the immune response. Similar studies revealed a counterregulatory role for IDO during leishmaniasis (restraining effector immune responses and parasite clearance), and no evident role for IDO in herpes simplex virus type 1 (HSV-1) infection. Thus, IDO plays biologically important roles in the host response to diverse intracellular infections, but the dominant nature of this role--antimicrobial or immunoregulatory--is pathogen-specific.

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“…Moreover, technical differences may also account for the discrepancies, since immunohistochemistry is a highly specialized procedure affected by many parameters such as antibody preparations, tissue processing and blocking steps. Sedlmayr et al 19 used the same monoclonal antibody to IDO as Takikawa et al 35 at dilutions between 1 : 500 and 1 : 1000, whereas Ho¨nig et al 22 used the same rabbit antiIDO polyclonal antibody as Munn et al 36 diluted to 1 : 1000. In this current study, after titration, mouse antihuman monoclonal antibody (clone 10.1) was found to be optimal at a dilution of 1 : 150.…”

Section: Groups Nmentioning

confidence: 99%

Indoleamine 2,3-dioxygenase levels at the normal and recurrent spontaneous abortion fetal–maternal interface

et al. 2013

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Objectives: To localize indoleamine 2,3-dioxygenase (IDO) mRNA and protein and to undertake a functional study at the first trimester fetal-maternal interface in order to determine whether the distribution and function of IDO are related to recurrent spontaneous abortion (RSA). Methods: Women undergoing legal pregnancy termination and women with RSA participated in this prospective study. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction were used to analyse levels of IDO protein and mRNA in placenta, decidua and HTR-8/SVneo cells. Culture medium collected from trophoblast villous explant or HTR-8/SVneo cell cultures was used to measure IDO activity in response to interferon (IFN)-g treatment. Results: A total of 40 healthy women and 26 women with RSA provided samples of placenta and decidua. For normal pregnancies, IDO protein and mRNA was identified in placental trophoblasts, invasive extravillous trophoblasts and decidual glandular epithelium. IFN-g significantly increased IDO activity in trophoblast villous explants and HTR-8/SVneo cells. Levels of IDO protein and mRNA in the placenta and decidua from normal pregnancies were significantly higher than in those from RSA. Conclusions: Decreased levels of IDO protein and mRNA in the placenta and decidua from RSA suggest an important role for IDO in the maintenance of normal pregnancy.

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Mechanism of interferon-gamma action. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity.

Cited by 429 publications

References 47 publications

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas

Opposing Biological Functions of Tryptophan Catabolizing Enzymes During Intracellular Infection

Indoleamine 2,3-dioxygenase levels at the normal and recurrent spontaneous abortion fetal–maternal interface

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