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Introduction Indoleamine 2,3‐dioxygenase (IDO) is an immunosuppressive tryptophan‐depleting enzyme expressed in nasopharyngeal carcinoma (NPC) tissue. However, IDO has not been reported in the peripheral blood of NPC patients. The aim of this study was to analyze, IDO1 and IDO2 messenger RNA (mRNA) expression, the kynurenine (Kyn) and tryptophan (Trp) plasma levels, their clinical values and their relationship with cytokine levels in NPC. Methods We evaluated IDO1 and IDO2 mRNA expression in peripheral blood mononuclear cells (PBMC) by quantitative real‐time PCR, plasma Trp and Kyn levels by HPLC, and cytokine levels by ELISA in 75 NPC patients and 51 healthy controls. Results Compared to controls, IDO1 mRNA expression was significantly upregulated and IDO2 mRNA expression was significantly downregulated in PBMC of patients. Also compared to controls, plasma Kyn levels and Kyn/Trp ratio were significantly higher in patients. At the time of diagnosis, the plasma Kyn/Trp ratio was associated with advanced cancer status and was an independent prognostic factor for worse disease‐specific survival. According to cancer stages, IDO1 mRNA expression was positively correlated with plasma Kyn/Trp ratio in patients with earlier stages (I–II–III) but negatively correlated in patients with the late‐stage cancer (IV). Tumor necrosis factor‐α, interleukin (IL)‐6 and IL‐10 levels were significantly higher in patients compared to controls. Moreover, and despite treatment, patients simultaneously carrying high plasma Kyn/Trp ratio and high plasma IL‐6 and IL‐10 levels at diagnosis died approximately 1 year after first diagnosis. Conclusion Measuring blood IDO mRNA expression and Kyn/Trp ratio at diagnosis could be a potential marker to evaluate NPC progression and predict survival outcome.

Nasopharyngeal carcinoma (NPC) is a disease that is closely associated with EBV infection. Toll-like receptor 9 is an important factor mediating the interaction between EBV and the host immune response. Any genetic (single nucleotide polymorphisms, SNPs) or expression variation in TLR9 gene may modify the ability of the receptor to respond correctly to viral infection as in NPC. This study is aimed at evaluating the effect of TLR9 functional polymorphisms (TLR9-1486 T/C and TLR9-1237 T/C) and TLR9 mRNA expression in NPC severity and progression at diagnosis and after treatment. This study included 322 patients with NPC. RFLP-PCR and real-time PCR were used to assess, respectively, the genotypes and the mRNA expression of TLR9 gene. The genotyping analysis showed that the presence of mutated allele -1237C (TLR9-1237 TC+CC) was associated with large tumor size (p = 0.017; OR (CI 95%) = 1.888 (1.11-3.19)) at diagnosis. After treatment, the -1237C allele was associated with a better chance of complete remission (p = 0.031, OR (CI 95%) = 0.486 (0.25-0.95)), a lower risk of distant metastasis (p = 0.028, OR (CI 95%) = 0.435 (0.18-1.02)), and a lower risk of death by NPC (p = 0.003, OR (CI 95%) = 0.20 (0.06-0.67)). Kaplan-Meier analysis showed that patients with -1237CC and -1237TC genotypes had a better overall survival (OVS) (p < 0.01) and distant metastasis-free survival (DMFS) (p < 0.05). A multivariate analysis revealed that TLR9-1237 T/C polymorphism was an independent prognostic factor in OVS (p = 0.02; HR = 0.244) and DMFS (p = 0.048; HR = 0.388). The transcriptomic analysis showed that the mRNA expression was reduced in patients with larger tumor size (T4) (p = 0.013) and advanced clinical stage (SIII-SIV) (p = 0.037). The TLR9 mRNA expression was inversely correlated with tumor size (p = 0.014; r = −0.314) at diagnosis. Our results indicated for the first time that the functional -1237 T/C polymorphism and mRNA expression of TLR9 gene may be considered as protective factors for NPC severity and progression.