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- Title
Accumulation of an Endogenous Tryptophan-Derived Metabolite in Colorectal and Breast Cancers.
- Authors
Puccetti, Paolo; Fallarino, Francesca; Italiano, Antoine; Soubeyran, Isabelle; MacGrogan, Gaetan; Debled, Marc; Velasco, Valerie; Bodet, Dominique; Eimer, Sandrine; Veldhoen, Marc; Prendergast, Georges C.; Platten, Michael; Bessede, Alban; Guillemin, Gilles J.
- 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 -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 -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 -kynurenine production. In colorectal cancer -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.
- Subjects
COLON cancer treatment; TRYPTOPHAN derivatives; BREAST cancer treatment; TUMOR treatment; IMMUNOSUPPRESSION; TUMOR antigens; CANCER immunotherapy
- Publication
PLoS ONE, 2015, Vol 10, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0122046