دورية أكاديمية
أعرض في EDS

Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas.

التفاصيل البيبلوغرافية
العنوان: Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas.
المؤلفون: Hariharan S; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Whitfield BT; Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Pirozzi CJ; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Pathology, Duke University Medical Center, Durham, NC, USA., Waitkus MS; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Brown MC; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Bowie ML; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Irvin DM; Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Roso K; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Pathology, Duke University Medical Center, Durham, NC, USA., Fuller R; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Hostettler J; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Dharmaiah S; Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gibson EA; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Briley A; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Mangoli A; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Fraley C; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Shobande M; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Stevenson K; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA., Zhang G; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Malgulwar PB; Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Roberts H; Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Roskoski M; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., Spasojevic I; PK/PD Core Laboratory, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.; Department of Medicine - Oncology, Duke University Medical Center, Durham, NC, USA., Keir ST; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA., He Y; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Department of Pathology, Duke University Medical Center, Durham, NC, USA., Castro MG; Department of Neurosurgery, University of Michigan Medical Center, Ann Arbor, MI, USA., Huse JT; Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. jhuse@mdanderson.org., Ashley DM; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. david.ashley@duke.edu.; Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. david.ashley@duke.edu.
المصدر: Nature communications [Nat Commun] 2024 Jan 25; Vol. 15 (1), pp. 730. Date of Electronic Publication: 2024 Jan 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Brain Neoplasms*/genetics , Brain Neoplasms*/metabolism , Glioma*/genetics , Glioma*/metabolism , Astrocytoma*/genetics, Humans ; X-linked Nuclear Protein/genetics ; Mutation ; Immunity, Innate/genetics ; Isocitrate Dehydrogenase/genetics ; Isocitrate Dehydrogenase/metabolism
مستخلص: Stimulating the innate immune system has been explored as a therapeutic option for the treatment of gliomas. Inactivating mutations in ATRX, defining molecular alterations in IDH-mutant astrocytomas, have been implicated in dysfunctional immune signaling. However, little is known about the interplay between ATRX loss and IDH mutation on innate immunity. To explore this, we generated ATRX-deficient glioma models in the presence and absence of the IDH1 R132H mutation. ATRX-deficient glioma cells are sensitive to dsRNA-based innate immune agonism and exhibit impaired lethality and increased T-cell infiltration in vivo. However, the presence of IDH1 R132H dampens baseline expression of key innate immune genes and cytokines in a manner restored by genetic and pharmacological IDH1 R132H inhibition. IDH1 R132H co-expression does not interfere with the ATRX deficiency-mediated sensitivity to dsRNA. Thus, ATRX loss primes cells for recognition of dsRNA, while IDH1 R132H reversibly masks this priming. This work reveals innate immunity as a therapeutic vulnerability of astrocytomas.
(© 2024. The Author(s).)
التعليقات: Update of: bioRxiv. 2023 Apr 21;:. (PMID: 37131619)
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معلومات مُعتمدة: R01 CA255788 United States CA NCI NIH HHS; R01 CA240338 United States CA NCI NIH HHS; TL1 TR003169 United States TR NCATS NIH HHS; UL1 TR003167 United States TR NCATS NIH HHS; P30 CA014236 United States CA NCI NIH HHS
المشرفين على المادة: EC 3.6.4.12 (X-linked Nuclear Protein)
EC 1.1.1.41 (Isocitrate Dehydrogenase)
EC 3.6.4.12 (ATRX protein, human)
EC 1.1.1.42. (IDH1 protein, human)
تواريخ الأحداث: Date Created: 20240125 Date Completed: 20240129 Latest Revision: 20240205
رمز التحديث: 20240205
مُعرف محوري في PubMed: PMC10810843
DOI: 10.1038/s41467-024-44932-w
PMID: 38272925
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-44932-w