Accumulation of an endogenous tryptophan-derived metabolite in colorectal and breast cancers

Paolo Puccetti, Francesca Fallarino, Antoine Italiano, Isabelle Soubeyran, Gaetan MacGrogan, Marc Debled, Valerie Velasco, Dominique Bodet, Sandrine Eimer, Marc Veldhoen, Georges C. Prendergast, Michael Platten, Alban Bessede, Gilles J. Guillemin

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30 Citations (Scopus)

Abstract

Tumor immune escape mechanisms are being regarded as suitable targets for tumor therapy. Among these, tryptophan catabolism plays a central role in creating an immunosuppressive environment, leading to tolerance to potentially immunogenic tumor antigens. Tryptophan catabolism is initiated by either indoleamine 2,3-dioxygenase (IDO-1/-2) or tryptophan 2,3-dioxygenase 2 (TDO2), resulting in biostatic tryptophan starvation and L-kynurenine production, which participates in shaping the dynamic relationship of the host's immune system with tumor cells. Current immunotherapy strategies include blockade of IDO-1/-2 or TDO2, to restore efficient antitumor responses. Patients who might benefit from this approach are currently identified based on expression analyses of IDO-1/-2 or TDO2 in tumor tissue and/or enzymatic activity assessed by kynurenine/tryptophan ratios in the serum. We developed a monoclonal antibody targeting L-kynurenine as an in situ biomarker of IDO-1/-2 or TDO2 activity. Using Tissue Micro Array technology and immunostaining, colorectal and breast cancer patients were phenotyped based on L-kynurenine production. In colorectal cancer L-kynurenine was not unequivocally associated with IDO-1 expression, suggesting that the mere expression of tryptophan catabolic enzymes is not sufficiently informative for optimal immunotherapy.

Original languageEnglish
Article numbere0122046
Pages (from-to)1-9
Number of pages9
JournalPLoS ONE
Volume10
Issue number4
DOIs
Publication statusPublished - 16 Apr 2015

Bibliographical note

Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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    Puccetti, P., Fallarino, F., Italiano, A., Soubeyran, I., MacGrogan, G., Debled, M., ... Guillemin, G. J. (2015). Accumulation of an endogenous tryptophan-derived metabolite in colorectal and breast cancers. PLoS ONE, 10(4), 1-9. [e0122046]. https://doi.org/10.1371/journal.pone.0122046