12 Sep Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of IDO1
Indoleamine 2,3- dioxygenase 1 (IDO1) is a cytosolic heme-containing enzyme that functions to catalyze tryptophan (Trp) degradation and kynurenine (Kyn) production, and the Trp:Kyn ratio reflects IDO1 activity. Tobacco carcinogens upregulate IDO1. Clinically, smoker patients with non-small-cell lung cancer (NSCLC) exhibited high IDO1 levels and low Trp/ Kyn ratios. In NSCLC patients, smokers with lower IDO1 responded better to anti-PD1 antibody treatment than those with higher IDO1. The data indicate that tobacco smoke induces IDO1 to catabolize Trp metabolism and immune suppression to promote carcinogenesis, and lower IDO1 might be a potential biomarker for anti-PD1 antibodies in smoker patients, whereas IDO1-high smoker patients might benefit from IDO1 inhibitors in combination with anti-PD1 antibodies. ( Ref: Liang F et al. Signal Transduct Target Ther. Sep 7, 2022)
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