Understanding the role of the kynurenine pathway in human breast cancer immunobiology

Benjamin Heng, Chai K. Lim, David B. Lovejoy, Alban Bessede, Laurence Gluch, Gilles J. Guillemin*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    92 Citations (Scopus)
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    Breast cancer (BrCa) is the leading cause of cancer related death in women. While current diagnostic modalities provide opportunities for early medical intervention, significant proportions of breast tumours escape treatment and metastasize. Gaining increasing recognition as a factor in tumour metastasis is the local immuno-surveillance environment. Following identification of the role played by the enzyme indoleamine dioxygenase 1 (IDO1) in mediating maternal foetal tolerance, the kynurenine pathway (KP) of tryptophan metabolism has emerged as a key metabolic pathway contributing to immune escape. In inflammatory conditions activation of the KP leads to the production of several immune-modulating metabolites including kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, picolinic acid and quinolinic acid. KP over-activation was first described in BrCa patients in the early 1960s. More evidence has since emerged to suggest that the IDO1 is elevated in advanced BrCa patients and is associated with poor prognosis. Further, IDO1 positive breast tumours have a positive correlation with the density of immune suppressive Foxp3+ T regulatory cells and lymph node metastasis. The analysis of clinical microarray data in invasive BrCa compared to normal tissue showed, using two microarray databank (cBioportal and TCGA), that 86.3% and 91.4% BrCa patients have altered KP enzyme expression respectively. Collectively, these data highlight the key roles played by KP activation in BrCa, particularly in basal BrCa subtypes where expression of most KP enzymes was altered. Accordingly, the use of KP enzyme inhibitors in addition to standard chemotherapy regimens may present a viable therapeutic approach.

    Original languageEnglish
    Pages (from-to)6506-6520
    Number of pages15
    Issue number6
    Publication statusPublished - 9 Feb 2016

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    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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