Targeting TDO in cancer immunotherapy.

Tryptophan-2,3-dioxygenase (TDO) is a homotetrameric heme-containing protein catalyzing the initial step in the kynurenine pathway, which oxidates the 2,3-double bond of the indole ring in L-tryptophan and catalyzes it into kynurenine (KYN). The upregulation of TDO results in a decrease in tryptophan and the accumulation of KYN and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence demonstrates that TDO is a promising therapeutic target in the anti-tumor process. Despite its growing popularity, there are only a few reviews focusing on TDO in tumors. Hence, we herein review the biological features and regulatory mechanisms of TDO. Additionally, we focus on the role of TDO in the anti-tumor immune response in different tumors. Finally, we also provide our viewpoint regarding the future developmental directions of TDO in cancer research, especially in relation to the development and application of TDO inhibitors as novel cancer treatments.

[A noninvasive model to predict histological liver cirrhosis in patients with chronic hepatitis B].

OBJECTIVE: To construct a noninvasive model to predict histological liver cirrhosis in patients with chronic hepatitis B. METHODS: 275 patients with chronic hepatitis B were divided into a training group (206 cases) and a validation group (69 cases). The constituent ratios of patients in the fibrosis stages S0-S3, fibrosis stage S4 (early cirrhosis) and active cirrhosis stage were calculated according to the liver biopsy results. 30 noninvasive variables, including age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), spleen-platelet ratio index (SRPI) and age-spleen-platelet ratio index (ASPRI), were analyzed by univariate analysis and multivariate logistic regression. Variables that were significantly different between patients with and without cirrhosis were used to construct a noninvasive prediction model, and the model was then tested in the validation group. RESULTS: (1) Of the 275 patients with chronic hepatitis B, 193 (70.2%) were in the fibrosis stages S0-S3, 42 (15.3%) in fibrosis stage S4, 40 (14.5%) in active cirrhosis stage. (2) There were 23 variables that are significantly different between patients with and without cirrhosis by univariate analysis. The 23 variables were further analyzed by multivariate logistic regression, and 4 independent factors, including international normalized ratio (INR), gamma glutamyltranspeptidase (GGT), ASPRI, hepatitis B e antigen (HBeAg) were used to construct a noninvasive prediction model. (3) By receiver operating characteristic curves (ROC) analysis, to discriminate patients in stages S0-S3 from patients in stage S4 and patients in active cirrhosis stage, the area under ROC (AUROC), cut-off value, sensitivity, specificity and accuracy of the model were 0.871, 0.458, 84.4%, 75.7%, and 79.7% respectively. To discriminate patients in active cirrhosis stage from patients in other stages, the AUROC, cut-off value, sensitivity, specificity and accuracy were 0.753, 0.526, 81.8%, 62.9%, and 67.4% respectively. There was no significant difference in AUROC between the training group and the validation group (P less than 0.05). CONCLUSION: INR, GGT, ASPRI and HBeAg are associated with early cirrhosis and active cirrhosis. Our model can be used to predict early cirrhosis and active cirrhosis.