Prognostic role of indoleamine 2,3-dioxygenase 1 expression in solid tumors: A systematic review and meta-analysis

Abstract

BackgroundAs an emerging immune checkpoint molecule, indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive rate-limiting enzyme in metabolism of tryptophan to kynurenine. The expression of IDO1 affected the prognosis of patients in cancers by regulating the kynurenine pathway, inhibiting the proliferation of T cells. However, the association between IDO1 and solid tumor prognosis was controversial. To further investigate the role of IDO1 expression in solid tumors, we conducted the systematic review and meta-analysis.MethodsWe searched the Web of Science, PubMed, Embase, and Cochrane Library databases and China National Knowledge Infrastructure (CNKI) to identify studies evaluating the prognostic value of IDO1 in solid tumors. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were extracted as the outcome. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by using the fixed-effect/random-effect model, while heterogeneity, publication bias, and sensitivity between studies were also analyzed.ResultsEighteen studies with 2,168 patients were included in this systematic review and meta-analysis. The results indicated that the high expression of IDO1 was associated with a shorter OS (n = 1926, HR = 1.60, 95% CI: 1.22–2.11, P = 0.001) and DFS (n = 327, HR = 2.65, 95% CI: 1.52–4.63, P = 0.001), while it was uncorrelated with PFS (n = 428, HR = 1.76, 95% CI: 0.99–3.14, P = 0.240). There was significant heterogeneity between studies on OS (I2 = 77.8%, P < 0.001). Subgroup analysis showed that age, gender, tumor type, follow-up period, and study quality were possible reasons for high heterogeneity. The result of the trim-and-fill method indicated that publication bias for OS had no impact on our results. Egger’s test suggested no publication bias for PFS (P = 0.553) and DFS (P = 0.273). Furthermore, sensitivity analysis indicated the result was stable.ConclusionHigh expression of IDO1 was associated with poor clinical outcomes, indicating that it could be a potential prognostic marker in various cancer types.

Immune-checkpoint gene expression and BCG response in non-muscle invasive bladder cancer

“…Addiotionally, IDO1 seems to promote epithelial-mesenchymal transition through PD-L1 pathway [ 52 ]. Zhang et al evaluated the prognostic role of IDO1 expression in solid tumors through a systematic review and meta-analysis and they found shorter Overall Survival associated with high expression of IDO1 , corroborating with our findings [ 53 ].…”

Tryptophan Metabolism in Developmental Origins of Health and Disease (DOHaD)

“…Accelerated tryptophan metabolism via IDO enzyme occurs in several disorders, such as neurodegeneration, cardiovascular diseases, infections and malignancies. Malignant cells can activate IDO enzyme expression [113] which is observed in many human cancers [114]. In tryptophan catabolism, the IDO enzyme has diverse biological roles in immune suppression and tumour progression [115].…”

“…To date, there are several inhibitors available that have already entered clinical trials [115]. A recent meta-analysis indicates that IDO expression may be a prognostic marker of cancer in various tissues and that its expression is a promising pharmaceutical target [113].…”

Breaking Barriers: Modulation of Tumor Microenvironment to Enhance Bacillus Calmette–Guérin Immunotherapy of Bladder Cancer

“…Kynurenine, an IDO product, activates the aryl hydrocarbon receptor (AhR), facilitating the differentiation of T cells into Tregs and contributing to immune tolerance [115]. The genetic makeup of individuals regulates IDO1 expression through the polymorphisms or mutations that regulate the IDO1 gene directly or modulate the regulatory pathways governing IDO1 expression [116][117][118]. Polymorphisms associated with heightened IDO1 activity, fostering a suppressive TME that is conductive of immune evasion [116][117][118], indicating their consideration in the therapeutic potential of IDO1-targeted interventions [119,120].…”

“…The genetic makeup of individuals regulates IDO1 expression through the polymorphisms or mutations that regulate the IDO1 gene directly or modulate the regulatory pathways governing IDO1 expression [116][117][118]. Polymorphisms associated with heightened IDO1 activity, fostering a suppressive TME that is conductive of immune evasion [116][117][118], indicating their consideration in the therapeutic potential of IDO1-targeted interventions [119,120]. Furthermore, chemotherapeutic agents can elevate IDO1 expression as a result of the cancer cell stress response [121,122].…”