Increased tryptophan degradation in patients with bronchus carcinoma

Abstract

Expression of tryptophan-degrading enzyme indoleamine (2,3)-dioxygenase in tumour tissue is proposed to represent an important tumour immunoescape mechanism. To further investigate the potential role of activated indoleamine (2,3)-dioxygenase in bronchus carcinoma, we examined serum tryptophan and kynurenine concentrations in nine patients with small cell lung cancer and in 27 patients with non-small cell lung cancer. Tryptophan metabolic changes were compared with markers of inflammation and immune activation namely C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and neopterin. Compared with controls, patients presented with lower tryptophan concentrations (P < 0.01) and with higher serum kynurenine to tryptophan ratios (P < 0.01), an index of tryptophan degradation. Also ESR and CRP and neopterin concentrations were increased in the patients (all P < 0.001), and there was a weak correlation between kynurenine to tryptophan ratio and ESR, CRP and neopterin concentrations. We conclude that in the majority of patients with non-small cell lung cancer and small cell lung cancer, enhanced tryptophan degradation can be observed. It seems to relate to an inflammatory response and may reflect activation of indoleamine (2,3)-dioxygenase at the tumour site. The capacity of the tumour to escape normal host immune defence may be influenced by tryptophan degradation. Results of this pilot study deserve further confirmation.

Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in stage III non-small cell lung cancer.

“…We found that IDO activity was higher in cancer patients than in healthy individuals, consistent with previous observations in lung cancer, 24,25,31 bladder cancer, hepatocellular carcinoma, renal cell Fischer's exact p = 0.0003). This difference may reflect a posttranscriptional regulation of IDO.…”

“…24,25 This said, how IDO activity changes of rapamycin (mTOR) and protein kinase C Θ (PKCΘ), thereby inhibiting autophagy. 8 In fact, IDO is overexpressed by many human cancers 9 and may serve as an escape mechanism from host immunity.…”

Pre-treatment effects of peripheral tumors on brain and behavior: Neuroinflammatory mechanisms in humans and rodents

“…IDO activity is associated with tumor induction and is often highly expressed in solid tumors (Munn & Mellor, 2013). Higher kynurenine/tryptophan ratios and lower tryptophan concentrations in blood compared to healthy controls have been reported in colorectal cancer, malignant melanoma, non-small cell and small cell lung cancer, ovarian cancer, endometrial cancer, vulvar cancer, and breast cancer patients (de Jong et al, 2011; Engin et al, 2010; Huang et al, 2002; Lyon et al, 2011; Sperner-Unterweger et al, 2011; Suzuki et al, 2010; Weinlich et al, 2007), although the opposite pattern was noted in a study of primary cervical cancer patients (Fotopoulou et al, 2011). Thus, it appears that increased IDO activity in peripheral blood is associated with many malignancies prior to treatment.…”

Circulating Biomarkers of Tryptophan and the Kynurenine Pathway and Lung Cancer Risk

“…The key enzymes in degradation of tryptophan through the kynurenine pathway, IDO and TDO, as well as downstream catabolites may influence the immune system (11,24), and thus affect cancer development and progression (7,8,10,12,17,18,25). KTR is considered an indirect marker of IDO activity and was in the current study associated with increased risk of lung cancer.…”

“…The kynurenine pathway ( Fig. 1), and in particular, the key enzymes involved, 2,3-dioxygenase (IDO) and 2,3-tryptophan dioxygenase (TDO), have been implicated in cancer-related immune escape (8,(10)(11)(12)(13). High IDO activity causes an increased conversion of tryptophan to its primary catabolite, kynurenine.…”