Degradation of essential amino acids by tumour cells is emerging as an important cancer evasion strategy. Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are rate-limiting enzymes in the kynurenine pathway, which catalyzes the conversion of the essential amino acid tryptophan to kynurenine. In IDO+ and TDO+ solid cancers, it has been shown that tryptophan catabolism is exploited as an important mechanism of immune escape. More recently, we have demonstrated that in haematological cancers a large proportion of AML patients have high levels of arginase 2 (ARG2) in the serum, which induces suppression of T cell proliferation and of hematopoietic stem cells (Mussai et al., Blood, 122:749, 2013).

However, little is known about how cancer cells expressing such amino acid-degrading enzymes remain resistant to local amino acid depletion, which exerts detrimental effects on other cell types, including T cells.

One possibility to account for the ability of tumour cells to overcome the effects of low amino acid availability in the microenvironment is by modifying their repertoire of amino acid transporters and up-regulating higher affinity amino acid transporters. In agreement with this hypothesis, we will present results demonstrating that tumour cells can compensate for local shortage of essential amino acids using mechanisms, which are not shared by adaptive and innate immune cells.