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Characterization of the selective indoleamine 2,3-dioxygenase-1 (IDO1) catalytic inhibitor EOS200271/PF-06840003 supports IDO1 as a critical resistance mechanism to PD-(L)1 blockade therapy

Abstract:

Tumors use Indoleamine 2,3-dioxygenase-1 (IDO1) as a major mechanism to induce an immunosuppressive microenvironment. IDO1 expression is upregulated in many cancers and considered to be a resistance mechanism to immune checkpoint therapies. IDO1 is induced in response to inflammatory stimuli such as IFN and promotes immune tolerance by depleting tryptophan and producing tryptophan catabolites including kynurenine in the tumor microenvironment. This leads to effector T-cell anergy and enhance...

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Publication status:
Published
Peer review status:
Peer reviewed
Version:
Accepted Manuscript

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Files:
Publisher copy:
10.1158/1535-7163.mct-17-1104

Authors


Driessens, G More by this author
Bartlett, D More by this author
Cauwenberghs, S More by this author
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Publisher:
American Association for Cancer Research Publisher's website
Journal:
Molecular cancer therapeutics Journal website
Volume:
17
Issue:
12
Pages:
2530-2542
Publication date:
2018-09-19
Acceptance date:
2018-09-12
DOI:
ISSN:
1538-8514 and 1535-7163
Pubs id:
pubs:921624
URN:
uri:0d4fbf62-5a29-4242-9a49-40407c657439
UUID:
uuid:0d4fbf62-5a29-4242-9a49-40407c657439
Local pid:
pubs:921624

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