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Microenvironment Tumor Metabolic Interactions Highlighted by qMSI: Application to the Tryptophan-Kynurenine Pathway in Immuno-Oncology

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Ait-Belkacem, Rima Bol, Vanesa Hamm, Gregory Schramme, Florence [UCL] Van den Eynde, Benoît [UCL] Gomes, Bruno

(eng) Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain. Here, we describe the detection, localization, and absolute quantitation of Trp and Kyn by quantitative mass spectrometry imaging (qMSI) in transfected murine tumor models expressing various levels of IDO1. Myeloid, glycolysis metabolic signatures, and correlation between IDO1 expression and Trp to Kyn conversion are also shown. High-definition IDO1 and GCN2 immunostainings overlaid with Kyn molecular images underline the tumor metabolism and heterogeneity. The development of immunotherapies such as IDO1 inhibitors requires a deep understanding of the immune system, the interplay of cancer cells, and biomarker characterization. Our data underline that qMSI allows the study of the spatial distribution and quantitation of endogenous immune metabolites for biology and pharmacology studies.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2017
Language Anglais
Journal information "SLAS discovery : advancing life sciences R & D" - Vol. 22, no. 10, p. 1182-1192 (2017)
Peer reviewed yes
Publisher SAGE Publications ((United States) Thousand Oaks, CA)
issn 2472-5552
e-issn 2472-5560
Publication status Publié
Affiliation UCL - SSS/DDUV/GECE - Génétique cellulaire
Keywords IDO1 ; Biomarker ; Kynurenine ; Quantitative MSI ; Tryptophan
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Bibliographic reference Ait-Belkacem, Rima ; Bol, Vanesa ; Hamm, Gregory ; Schramme, Florence ; Van den Eynde, Benoît ; et. al. Microenvironment Tumor Metabolic Interactions Highlighted by qMSI: Application to the Tryptophan-Kynurenine Pathway in Immuno-Oncology. In: SLAS discovery : advancing life sciences R & D, Vol. 22, no. 10, p. 1182-1192 (2017)
Permanent URL http://hdl.handle.net/2078.1/185805