Abstract
BackgroundIndoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the metabolism of tryptophan into kynurenine. It is considered to be an immunosuppressive molecule that plays an important role in the development of tumors. However, the association between IDO and solid tumor prognosis remains unclear. Herein, we retrieved relevant published literature and analyzed the association between IDO expression and prognosis in solid tumors.MethodsStudies related to IDO expression and tumor prognosis were retrieved using PMC, EMbase and web of science database. Overall survival (OS), time to tumor progression (TTP) and other data in each study were extracted. Hazard ratio (HR) was used for analysis and calculation, while heterogeneity and publication bias between studies were also analyzed.ResultsA total of 31 studies were included in this meta-analysis. Overall, high expression of IDO was significantly associated with poor OS (HR 1.92, 95% CI 1.52–2.43, P < 0.001) and TTP (HR 2.25 95% CI 1.58–3.22, P < 0.001). However, there was significant heterogeneity between studies on OS (I2 = 81.1%, P < 0.001) and TTP (I2 = 54.8%, P = 0.007). Subgroup analysis showed lower heterogeneity among prospective studies, studies of the same tumor type, and studies with follow-up periods longer than 45 months.ConclusionsThe high expression of IDO was significantly associated with the poor prognosis of solid tumors, suggesting that it can be used as a biomarker for tumor prognosis and as a potential target for tumor therapy.
Highlights
Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the metabolism of tryptophan into kynurenine
The final 31 studies included a total of 3939 patients for meta-analysis to analyze the association between IDO expression and prognosis in solid tumor patients [14–44]
The 31 studies included in this meta-analysis were derived from 10 countries, 6 studies originating from Europe, 18 from Asia (10 from China; and 8 from Japan), 2 from Africa (Tunisia), 3 from USA, 2 from Australia
Summary
Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the metabolism of tryptophan into kynurenine. The association between IDO and solid tumor prognosis remains unclear. We retrieved relevant published literature and analyzed the association between IDO expression and prognosis in solid tumors. Indoleamine 2,3-dioxygenase (IDO) is an intracellular and immunosuppressive rate-limiting enzyme in metabolism of tryptophan to kynurenine [1]. The main metabolic pathway for tryptophan in IDO can exert immunosuppressive effects through a variety of mechanisms. The main metabolite of tryptophan degradation, kynurenine, has a direct toxic effect on T cells and induces T cell apoptosis. By activating aryl hydrocarbon receptors, kynurenine can regulate the differentiation direction of Th17/Treg cells, thereby promoting the balanced differentiation of Th17/Treg to Treg cells [3–5]
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