The indoleamine 2,3-dioxygenase (IDO) enzyme can act as an immunoregulator by 
inhibiting T cell function via the degradation of the essential amino acid 
tryptophan (trp) into kynurenine (kyn) and its derivates. The kyn/trp ratio in 
serum is a prognostic factor for cervical cancer patients; however, information 
about the relationship between serum levels and IDO expression in the tumor is 
lacking. IDO expression was studied in 71 primary and 14 paired metastatic 
cervical cancer samples by various immunohistochemical (IHC) techniques, 
including 7-color fluorescent multiparameter IHC, and the link between the 
concentration of IDO metabolites in serum, clinicopathological characteristics, 
and the presence of (proliferating) T cells (CD8, Ki67, and FoxP3) was examined. 
In addition, we compared the relationships between IDO1 and IFNG gene expression 
and clinical parameters using RNAseq data from 144 cervical tumor samples 
published by The Cancer Genome Atlas (TCGA). Here, we demonstrate that patchy 
tumor IDO expression is associated with an increased systemic kyn/trp ratio in 
cervical cancer (P = 0.009), whereas marginal tumor expression at the interface 
with the stroma is linked to improved disease-free (DFS) (P = 0.017) and 
disease-specific survival (P = 0.043). The latter may be related to T cell 
infiltration and localized IFNγ release inducing IDO expression. Indeed, TCGA 
analysis of 144 cervical tumor samples revealed a strong and positive 
correlation between IDO1 and IFNG mRNA expression levels (P < 0.001) and a 
significant association with improved DFS for high IDO1 and IFNG transcript 
levels (P = 0.031). Unexpectedly, IDO+ tumors had higher CD8+Ki67+ T cell rates 
(P = 0.004). Our data thus indicate that the serum kyn/trp ratio and IDO 
expression in primary tumor samples are not clear-cut biomarkers for prognosis 
and stratification of patients with early stage cervical cancer for clinical 
trials implementing IDO inhibitors. Rather, a marginal IDO expression pattern in 
the tumor dominantly predicts favorable outcome, which might be related to IFNγ 
release in the cervical tumor microenvironment.