دورية أكاديمية
أعرض في EDS

An adverse tumor-protective effect of IDO1 inhibition.

التفاصيل البيبلوغرافية
العنوان: An adverse tumor-protective effect of IDO1 inhibition.
المؤلفون: Kenski JCN; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Huang X; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Vredevoogd DW; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., de Bruijn B; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Traets JJH; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Ibáñez-Molero S; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Schieven SM; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., van Vliet A; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Krijgsman O; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Kuilman T; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Pozniak J; Laboratory for Molecular Cancer Biology, Center for Cancer Biology, VIB, Leuven, Belgium; Laboratory for Molecular Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium., Loayza-Puch F; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Terry AM; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Müller J; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Logtenberg MEW; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., de Bruijn M; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Levy P; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Körner PR; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Goding CR; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Headington, OX OX3 7DQ, UK., Schumacher TN; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Marine JC; Laboratory for Molecular Cancer Biology, Center for Cancer Biology, VIB, Leuven, Belgium; Laboratory for Molecular Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium., Agami R; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands., Peeper DS; Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: d.peeper@nki.nl.
المصدر: Cell reports. Medicine [Cell Rep Med] 2023 Feb 21; Vol. 4 (2), pp. 100941.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2020]-
مواضيع طبية MeSH: Tryptophan* , Melanoma*/pathology, Humans ; Interferon-gamma/metabolism ; T-Lymphocytes/metabolism ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics
مستخلص: By restoring tryptophan, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors aim to reactivate anti-tumor T cells. However, a phase III trial assessing their clinical benefit failed, prompting us to revisit the role of IDO1 in tumor cells under T cell attack. We show here that IDO1 inhibition leads to an adverse protection of melanoma cells to T cell-derived interferon-gamma (IFNγ). RNA sequencing and ribosome profiling shows that IFNγ shuts down general protein translation, which is reversed by IDO1 inhibition. Impaired translation is accompanied by an amino acid deprivation-dependent stress response driving activating transcription factor-4 (ATF4) high /microphtalmia-associated transcription factor (MITF) low transcriptomic signatures, also in patient melanomas. Single-cell sequencing analysis reveals that MITF downregulation upon immune checkpoint blockade treatment predicts improved patient outcome. Conversely, MITF restoration in cultured melanoma cells causes T cell resistance. These results highlight the critical role of tryptophan and MITF in the melanoma response to T cell-derived IFNγ and uncover an unexpected negative consequence of IDO1 inhibition.
Competing Interests: Declaration of interests D.S.P. is co-founder, shareholder, and advisor of Immagene, which is unrelated to this study.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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فهرسة مساهمة: Keywords: IDO1; IDO1 inhibition; IFNgamma; MITF; T cells; clinical trial; immunotherapy; melanoma; translation
المشرفين على المادة: 8DUH1N11BX (Tryptophan)
82115-62-6 (Interferon-gamma)
0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
تواريخ الأحداث: Date Created: 20230222 Date Completed: 20230224 Latest Revision: 20230326
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC9975322
DOI: 10.1016/j.xcrm.2023.100941
PMID: 36812891
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-3791
DOI:10.1016/j.xcrm.2023.100941