Accumulation of an endogenous tryptophan-derived metabolite in colorectal and breast cancers
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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
16 April 2015
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| In: |
PLOS ONE
Year: 2015, Volume: 10, Issue: 4 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0122046 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pone.0122046 Verlag, kostenfrei, Volltext: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122046 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 11.07.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0122046 |