[A new mechanism of tumor resistance to the immune system, based on tryptophan breakdown by indoleamine 2,3-dioxygenase]

Abstract

T lymphocytes represent the main effectors of the immune response that can lead to tumor rejection, which represents the aim of various approaches of immunotherapy that are currently tested. However, in many cases, tumor cells appear to resist immune rejection. We have recently uncovered a new mechanism of tumoral immune resistance based on the expression by tumor cells of indoleamine 2,3-dioxygenase (IDO), an enzyme that rapidly degrades tryptophan, an amino acid that is crucial to sustain proliferation of T lymphocytes. We showed that most human tumors constitutively express IDO. We also observed that expression of IDO by immunogenic mouse tumor cells, prevents their rejection by pre-immunized mice. This effect is accompanied by a lack of accumulation of specific T cells at the tumor site, and can be partly reverted by systemic treatment of mice with an inhibitor of IDO, in the absence of noticeable toxicity. These results suggest that the efficacy of therapeutic vaccination of cancer patients might be improved by concomitant administration of an IDO inhibitor.