title: Accumulation of an endogenous tryptophan-derived metabolite in colorectal and breast cancers.
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.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Soubeyran
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
authors.forename: Gaetan
authors.initials: G
authors.lastname: MacGrogan
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Debled
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Velasco
authors.affiliation: ImmuSmol, Pessac, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bodet
authors.affiliation: Histology and Molecular Pathology of Tumors Laboratory EA 2406, University Bordeaux Segalen, Bordeaux, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Eimer
authors.affiliation: Laboratory for Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Veldhoen
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, United states of America.
authors.forename: Georges C
authors.initials: GC
authors.lastname: Prendergast
authors.affiliation: CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany; Department of Neurooncology, University Hospital, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.affiliation: ImmuSmol, Pessac, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Bessede
authors.affiliation: Macquarie University, Faculty of Medicine, Neuroinflammation group, Sydney, New South Wales, Australia; Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D006801:Humans; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D014364:Tryptophan