Prognostic value of indoleamine 2,3-dioxygenase activity and expression in nasopharyngeal carcinoma

Ben-Haj-Ayed, Ahlem; Moussa, Adnène; Ghedira, Randa; Gabbouj, Sallouha; Miled, Souad; Bouzid, Nadia; Tebra-Mrad, Sameh; Bouaouina, Noureddine; Chouchane, Lotfi; Zakhama, Abdelfattah; Hassen, Elham

doi:10.1016/j.imlet.2015.11.012

Cited by 34 publications

(28 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple immunosuppressive mechanisms in the tumor microenvironment can impair the functions of tumor-infiltrating lymphocytes. One of these immunosuppressive mechanisms is mediated by the IDO enzyme [27]. In 1998, Munn et al found that IDO1 could prevent fetus rejection by allowing maternal-fetal immune tolerance in the mouse placenta [36].…”

Section: Discussionmentioning

confidence: 99%

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme catalyzing the initial and rate-limiting steps in the kynurenine pathway, which converts tryptophan into kynurenine. Upregulation of IDO1 decreases tryptophan levels and increases the accumulation of kynurenine and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence has shown that IDO1 is highly expressed in various cancer types and associated with poor prognosis of cancer patients. However, the results were inconsistent. Methods: We searched the Web of Science, PubMed, Embase and Cochrane library databases to identify studies evaluating the prognostic value of IDO1 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using fixed-effects/random-effects models. Results: This systematic review and meta-analysis included 2706 patients from 24 articles. The results indicated a shorter overall survival in patients with high expression of IDO1 (hazard ratio [HR] = 2.03, 95% confidence interval [CI]: 1.56-2.63). Furthermore, disease-free survival was worse in patients with high expression of IDO1 (HR = 2.47, 95% CI: 1.46-4.20). Additionally, the pooled odds ratios (ORs) showed that increased IDO1 was significantly associated with tumor differentiation (OR = 1.81, 95% CI: 1.05-3.12), distant metastasis (OR = 1.45, 95% CI: 1.02-2.06), and poor clinical stage (OR = 1.89, 95% CI: 1.13-3.17). However, no significant correlation was observed of increased IDO1 expression with age, sex, lymph node metastasis, and tumor size. Conclusion: High expression of IDO1 is associated with poor clinical outcomes. IDO1 could serve as a biomarker of prognosis and a potential predictive factor of clinicopathology in various cancers. Further studies should be performed to verify the clinical utility of IDO1 in human solid tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…[6910] Overexpression of IDO has been identified correlating with poor clinical outcome in some cancer types, including breast, gastric, nasopharyngeal, and liver cancers. [11121314] However, the expression of IDO in pancreatic cancer and its prognostic value on pancreatic cancer has not been intensively studied.…”

Section: Introductionmentioning

confidence: 99%

Expression and Prognostic Value of Indoleamine 2,3-dioxygenase in Pancreatic Cancer

Zhang

Tan

et al. 2017

Chinese Medical Journal

View full text Add to dashboard Cite

Background:Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer.Methods:We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ). We performed immunohistochemical staining and Western blot analysis for IDO expression in both pancreatic cancer and normal pancreas tissues obtained from Chinese PLA General Hospital from July 2012 to December 2013. Survival analysis was performed to correlate IDO expression and histopathologic parameters with overall survival. The Kaplan-Meier method and Cox proportional hazards regression model were conducted.Results:PANC-1, CFPAC-1, and BxPC-3 cell lines expressed IDO at the protein level, and the relative expression amount increased after stimulation with 500 U/ml IFN-γ. Immunohistochemical analysis results revealed that high IDO expression was observed in 59% of pancreatic adenocarcinoma tissues. Compared with normal pancreatic tissues, pancreatic adenocarcinoma showed significantly higher IDO expression levels, especially among patients with high tumor node metastasis (TNM) stages (χ2 = 4.550, P = 0.030), poor histological differentiation (χ2 = 5.690, P = 0.017), and lymph node metastasis (χ2 = 4.340 P = 0.037). Kaplan-Meier survival curves showed that high IDO expression was correlated with low survival rates (hazard ratio [HR] = 0.49 P = 0.009). Multivariate analysis using Cox proportional hazards model indicated that lymph node metastasis (HR = 0.35 P = 0.010) and IDO expression (HR = 0.42 P = 0.020) were two independent prognostic predictors of pancreatic adenocarcinoma.Conclusions:The study confirmed that high IDO expression in pancreatic adenocarcinoma was related to poor prognosis of patients. These findings provided evidence that IDO was involved in pancreatic adenocarcinoma progression and might serve as a relevant therapeutic target.

show abstract

“…Although L. johnsonii N6.2 was found and characterized in regards to its correlation with reduced T1D onset, it has the potential to expand its beneficial functions into the realm of other chronic diseases. IDO is an immunoregulatory enzyme whose altered activity has been observed in a multitude of diseases, including autoimmunity and cancer [135][136][137]. L. johnsonii N6.2 has the ability to regulate IDO activity by inactivating its redox-sensitive heme centers through H 2 O 2 production [130].…”

Section: Figure 4 Most Accurately Summarizes the Work Our Group Has Dmentioning

confidence: 99%

The Synergistic Contribution of Lactobacillus and Dietary Phytophenols in Host Health

Kling¹,

Marcial²,

Roberson³

et al. 2016

Probiotics and Prebiotics in Human Nutrition and Health

View full text Add to dashboard Cite

Phytophenols are found ubiquitously among all plants. They are important in diets rich in fruits and vegetables because these compounds provide health benefits to the host, ultimately decreasing the incidence of chronic diseases. These compounds act as natural antioxidants and provide anti-inflammatory, antiviral, antibiotic, and antineoplastic properties. Reactive oxygen species (ROS) are produced under normal physiological functions, and low/moderate levels are required for cellular turnover and signaling. However, when ROS levels become too high, oxidative stress can occur. Phytophenols quench ROS and ultimately avoid the damaging effects ROS elicit on the cell. The highest source of bioavailable phytophenols comes from our diet as a component usually esterified in plant fiber. For phytophenols to be absorbed by the body, they must be released by esterases, or other related enzymes. The highest amount of esterase activity comes from the gastrointestinal (GI) microbiota; therefore, the host requires the activity of mutualistic bacteria in the GI tract to release absorbable phytophenols. For this reason, mutualistic bacteria have been investigated for beneficial properties in the host. Our laboratory has begun studying the interaction of Lactobacillus johnsonii N6.2 with the host since it was found to be negatively correlated with type 1 diabetes (T1D). Analyses of this strain have revealed two important characteristics: (1) It has the ability to release phytophenols from dietary fiber through the secretion of two strong cinnamoyl esterases and (2) L. johnsonii also has the ability to generate significant amounts of H 2 O 2 , controlling the activity of indoleamine 2,3-dioxygenase (IDO), an immunomodulatory enzyme.

show abstract

Prognostic value of indoleamine 2,3-dioxygenase activity and expression in nasopharyngeal carcinoma

Cited by 34 publications

References 48 publications

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

Expression and Prognostic Value of Indoleamine 2,3-dioxygenase in Pancreatic Cancer

The Synergistic Contribution of Lactobacillus and Dietary Phytophenols in Host Health

Contact Info

Product

Resources

About