Canine mast cell tumour cells regulate tryptophan catabolism via the expression of indoleamine 2,3-dioxygenase

Indoleamine 2,3-deoxygenase (IDO) produced by cancer cells catabolizes tryptophan (TRP) to kynurenine (KYN) in the environment, resulting induction of cancer immune escape through induction of T cell anergy and enhancement of regulatory T cells. Recently, inhibition of IDO has been recognized as one of therapeutic strategies for human neoplastic diseases. However, there have been few reports about IDO-expressing cancers in dogs. In this study, we attempted to examine whether canine mast cell tumour (MCT) cells express IDO and modulate the concentration of TRP and KYN in the environment. BR, MPT-1.2, and MPT-3 cells were used as canine MCT cells. Expression of IDO was examined with RT-PCR and western blotting. Concentrations of TRP and KYN in the culture medium after incubation with canine MCT cells were detected with liquid chromatographytandem mass spectrometry. The expression of mRNA and protein of IDO were confirmed in all samples extracted from canine MCT cells. TRP concentration in the culture medium was decreased and that of KYN was increased on incubation with canine MCT cells. The ratio of KYN/TRP, widely considered to represent IDO activity, was also significantly elevated. Moreover, treatment with an IDO inhibitor L-1-methyl-tryptophan (L-1MT) clearly diminished the elevation of KYN/TRP ratio induced by the incubation with canine MCT cells. Our results indicate that canine MCT cells could directly regulate the concentrations of TRP and KYN through expressing IDO, suggesting that canine MCT have an immune escape ability. Therefore, inhibition of IDO might be a novel strategy for the treatment of dogs with MCT.

Automated summary

Canine mast cell tumor cells can directly regulate the concentrations of TRP and KYN by expressing IDO, indicating an immune escape ability.