Introduction: Indoleamine-2,3-dioxygenase (IDO) converts L-tryptophan (T) to L-kynurenine (K) resulting in an immunosuppressive microenvironment. Aim of the current study is to evaluate in patients with neuroendocrine tumor (NET): 1) T and K concentrations; 2) correlation with clinical outcome; 3) relationship between IDO activity and inflammatory cytokines.
Methods: A cross-sectional study was performed to investigate the IDO pathway in patients in follow-up for NET. Clinico-pathological features, serum levels of K and T through liquid chromatography and serum assay of cytokines (IL-6, IL-10, IL-17A, IL-22, IL-23, TNF-α) through MAGPIX were evaluated.
Results: 78 NET patients were enrolled (66 lung, 12 pancreatic): 69.2% were in postoperative remission, 14.1% in stable disease and 16.7% in disease progression. T was significantly lower in patients older than 65 years (p=0.003). K and T were significantly lower in patients with progression (p=0.03, p=0.004, respectively). T was an independent predictor factor of progression in multivariable analysis (p=0.041). A cut-off of 7.74 μg/ml significantly differentiates patients with progression and those with stable disease. IL-6 and IL-10 were significantly associated with tumor progression on univariate analysis (p=0.005, p=0.001, respectively), but not at the multivariable. A statistically significant negative correlation was found between T and IL-10 (r=-0.366, p-value=0.04).
Conclusion: The K/T pathway may play a role as a potential predictor of tumor progression in NET. These findings need to be validated in large prospective studies investigating its metabolites as both prognostic and predictive factors for treatment response.
The Author(s). Published by S. Karger AG, Basel.