TY - JOUR
T1 - Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma.
AU - Rad Pour, Soudabeh
AU - Morikawa, Hiromasa
AU - Kiani, Narsis A.
AU - Gomez-Cabrero, David
AU - Hayes, Alistair
AU - Zheng, Xiaozhong
AU - Pernemalm, Maria
AU - Lehtiö, Janne
AU - Mole, Damian J.
AU - Hansson, Johan
AU - Eriksson, Hanna
AU - Tegner, Jesper
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank Peri Noori, the laboratory managers, and all the lab members for their valuable comments. We thank Pernilla Appelquist for their editorial support.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/661828
UR - https://www.frontiersin.org/article/10.3389/fonc.2020.00051/full
UR - http://www.scopus.com/inward/record.url?scp=85079782029&partnerID=8YFLogxK
U2 - 10.3389/fonc.2020.00051
DO - 10.3389/fonc.2020.00051
M3 - Article
C2 - 32117720
SN - 2234-943X
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
ER -