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Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma

Authors :
Soudabeh Rad Pour
Hiromasa Morikawa
Narsis A. Kiani
David Gomez-Cabrero
Alistair Hayes
Xiaozhong Zheng
Maria Pernemalm
Janne Lehtiö
Damian J. Mole
Johan Hansson
Hanna Eriksson
Jesper Tegnér
Source :
Frontiers in Oncology, Vol 10 (2020)
Publication Year :
2020
Publisher :
Frontiers Media S.A., 2020.

Abstract

Dysregulation of the kynurenine pathway has been regarded as a mechanism of tumor immune escape by the enzymatic activity of indoleamine 2, 3 dioxygenase and kynurenine production. However, the immune-modulatory properties of other kynurenine metabolites such as kynurenic acid, 3-hydroxykynurenine, and anthranilic acid are poorly understood. In this study, plasma from patients diagnosed with metastatic cutaneous malignant melanoma (CMM) was obtained before (PRE) and during treatment (TRM) with inhibitors of mitogen-activated protein kinase pathway (MAPKIs). Immuno-oncology related protein profile and kynurenine metabolites were analyzed by proximity extension assay (PEA) and LC/MS-MS, respectively. Correlation network analyses of the data derived from PEA and LC/MS-MS identified a set of proteins that modulate the differentiation of Th1 cells, which is linked to 3-hydroxykynurenine levels. Moreover, MAPKIs treatments are associated with alteration of 3-hydroxykynurenine and 3hydroxyanthranilic acid (3HAA) concentrations and led to higher “CXCL11,” and “KLRD1” expression that are involved in T and NK cells activation. These findings imply that the kynurenine pathway is pathologically relevant in patients with CMM.

Details

Language :
English
ISSN :
2234943X
Volume :
10
Database :
Directory of Open Access Journals
Journal :
Frontiers in Oncology
Publication Type :
Academic Journal
Accession number :
edsdoj.3a931a5829443e5bdad59c2b11dd4a5
Document Type :
article
Full Text :
https://doi.org/10.3389/fonc.2020.00051