In fact, given that Trp depletion following IDO or TDO induction in vivo and not in closed in vitro culture systems never reaches >60% of plasma values (averaged 60 μM) [5] and the huge rise in tumoral [Trp] in experimental in vivo models that is twice as high as plasma levels [75], it is more likely that the Trp depletion in the tumoral microenvironment to levels <10 μM is not the sole result of IDO/TDO induction, but could additionally involve a Kyn inhibition of Trp uptake. This evidence concerns the gene IDO1 and tricho-dento-osseous syndrome.