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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
25 Jan 2024
Historique:
received: 24 04 2023
accepted: 10 01 2024
medline: 26 1 2024
pubmed: 26 1 2024
entrez: 25 1 2024
Statut: epublish

Résumé

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

Identifiants

pubmed: 38272925
doi: 10.1038/s41467-024-44932-w
pii: 10.1038/s41467-024-44932-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

730

Subventions

Organisme : NCI NIH HHS
ID : R01 CA255788
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA255788
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA255788
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA240338
Pays : United States

Informations de copyright

© 2024. The Author(s).

Références

Ostrom, Q. T., Cioffi, G., Waite, K., Kruchko, C. & Barnholtz-Sloan, J. S. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2014–2018. Neuro. Oncol. 23, iii1–iii105 (2021).
pubmed: 34608945 pmcid: 8491279 doi: 10.1093/neuonc/noab200
Cancer Genome Atlas Research, N. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008).
doi: 10.1038/nature07385
Louis, D. N. et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro. Oncol. 23, 1231–1251 (2021).
pubmed: 34185076 pmcid: 8328013 doi: 10.1093/neuonc/noab106
Whitfield, B. T. & Huse, J. T. Classification of adult-type diffuse gliomas: impact of the World Health Organization 2021 update. Brain Pathol. 32, e13062 (2022).
pubmed: 35289001 pmcid: 9245936 doi: 10.1111/bpa.13062
Weller, M. et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat. Rev. Clin. Oncol. 18, 170–186 (2021).
pubmed: 33293629 doi: 10.1038/s41571-020-00447-z
Mohile, N. A. et al. Therapy for diffuse astrocytic and oligodendroglial tumors in adults: ASCO-SNO guideline. J. Clin. Oncol. 40, 403–426 (2022).
pubmed: 34898238 doi: 10.1200/JCO.21.02036
Waldman, A. D., Fritz, J. M. & Lenardo, M. J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20, 651–668 (2020).
pubmed: 32433532 pmcid: 7238960 doi: 10.1038/s41577-020-0306-5
Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010).
pubmed: 20525992 pmcid: 3549297 doi: 10.1056/NEJMoa1003466
Reardon, D. A. et al. Effect of Nivolumab vs Bevacizumab in patients with recurrent glioblastoma: the CheckMate 143 phase 3 randomized clinical trial. JAMA Oncol. 6, 1003–1010 (2020).
pubmed: 32437507 doi: 10.1001/jamaoncol.2020.1024
Lang, F. F. et al. Phase I study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: replication and immunotherapeutic effects in recurrent malignant glioma. J. Clin. Oncol. 36, 1419–1427 (2018).
pubmed: 29432077 pmcid: 6075856 doi: 10.1200/JCO.2017.75.8219
Desjardins, A. et al. Recurrent glioblastoma treated with recombinant poliovirus. N. Engl. J. Med. 379, 150–161 (2018).
pubmed: 29943666 pmcid: 6065102 doi: 10.1056/NEJMoa1716435
Fudaba, H. & Wakimoto, H. Oncolytic virus therapy for malignant gliomas: entering the new era. Expert Opin. Biol. Ther. 23, 269–282 (2023).
pubmed: 36809883 doi: 10.1080/14712598.2023.2184256
Brown, M. C. et al. Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling. Nat. Commun. 12, 1–16 (2021).
doi: 10.1038/s41467-021-22088-1
Kaufman, H. L., Kohlhapp, F. J. & Zloza, A. Oncolytic viruses: a new class of immunotherapy drugs. Nat. Rev. Drug Discov. 14, 642–662 (2015).
pubmed: 26323545 pmcid: 7097180 doi: 10.1038/nrd4663
Fitzgerald, K. A. et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4, 491–496 (2003).
pubmed: 12692549 doi: 10.1038/ni921
Kato, H. et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441, 101–105 (2006).
pubmed: 16625202 doi: 10.1038/nature04734
Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413, 732–738 (2001).
pubmed: 11607032 doi: 10.1038/35099560
Ishikawa, H., Ma, Z. & Barber, G. N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461, 788–792 (2009).
pubmed: 19776740 pmcid: 4664154 doi: 10.1038/nature08476
Cancer Genome Atlas Research, N. et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N. Engl. J. Med. 372, 2481–2498 (2015).
doi: 10.1056/NEJMoa1402121
Haase, S. et al. Mutant ATRX: uncovering a new therapeutic target for glioma. Expert Opin. Ther. Targets 22, 599–613 (2018).
pubmed: 29889582 pmcid: 6044414 doi: 10.1080/14728222.2018.1487953
Pan, D. et al. A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science 359, 770–775 (2018).
pubmed: 29301958 pmcid: 5953516 doi: 10.1126/science.aao1710
Griffin, G. K. et al. Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity. Nature 595, 309–314 (2021).
pubmed: 33953401 pmcid: 9166167 doi: 10.1038/s41586-021-03520-4
Babikir, H. et al. ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma. Genome Biol. 22, 311 (2021).
pubmed: 34763709 pmcid: 8588616 doi: 10.1186/s13059-021-02535-4
Hu, C. et al. ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma. Neuro. Oncol. 24, 888–900 (2022).
pubmed: 34951647 doi: 10.1093/neuonc/noab292
Amankulor, N. M. et al. Mutant IDH1 regulates the tumor-associated immune system in gliomas. Genes Dev. 31, 774–786 (2017).
pubmed: 28465358 pmcid: 5435890 doi: 10.1101/gad.294991.116
Venteicher, A. S. et al. Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. Science (New York, N.Y.) 355, eaai8478 (2017).
pubmed: 28360267 doi: 10.1126/science.aai8478
Tirosh, I. et al. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature 539, 309–313 (2016).
pubmed: 27806376 pmcid: 5465819 doi: 10.1038/nature20123
Hambardzumyan, D., Amankulor, N. M., Helmy, K. Y., Becher, O. J. & Holland, E. C. Modeling adult gliomas using RCAS/t-va technology. Transl. Oncol. 2, 89–95 (2009).
pubmed: 19412424 pmcid: 2670576 doi: 10.1593/tlo.09100
Dyer, M. A., Qadeer, Z. A., Valle-Garcia, D. & Bernstein, E. ATRX and DAXX: mechanisms and mutations. Cold Spring Harb. Perspect Med. 7, a026567 (2017).
pubmed: 28062559 pmcid: 5334245 doi: 10.1101/cshperspect.a026567
Kirby, A. J. & Finnerty, G. T. New strategies for managing adult gliomas. J. Neurol. 268, 3666–3674 (2021).
pubmed: 32542524 doi: 10.1007/s00415-020-09884-3
Mukherjee, J. et al. Mutant IDH1 cooperates with ATRX loss to drive the alternative lengthening of telomere phenotype in glioma. Cancer Res. 78, 2966–2977 (2018).
pubmed: 29545335 pmcid: 10578296 doi: 10.1158/0008-5472.CAN-17-2269
Kohanbash, G. et al. Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas. J. Clin. Invest. 127, 1425–1437 (2017).
pubmed: 28319047 pmcid: 5373859 doi: 10.1172/JCI90644
Pirozzi, C. J. & Yan, H. The implications of IDH mutations for cancer development and therapy. Nat. Rev. Clin. Oncol. 18, 645–661 (2021).
pubmed: 34131315 doi: 10.1038/s41571-021-00521-0
Waitkus, M. S., Diplas, B. H. & Yan, H. Biological role and therapeutic potential of IDH mutations in cancer. Cancer Cell 34, 186–195 (2018).
pubmed: 29805076 pmcid: 6092238 doi: 10.1016/j.ccell.2018.04.011
Golub, D. et al. Mutant isocitrate dehydrogenase inhibitors as targeted cancer therapeutics. Front Oncol. 9, 417 (2019).
pubmed: 31165048 pmcid: 6534082 doi: 10.3389/fonc.2019.00417
Pusch, S. et al. Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo. Acta Neuropathol. 133, 629–644 (2017).
pubmed: 28124097 doi: 10.1007/s00401-017-1677-y
Wick, A. et al. Phase I assessment of safety and therapeutic activity of BAY1436032 in patients with IDH1-mutant solid tumors. Clin. Cancer Res. 27, 2723–2733 (2021).
pubmed: 33622704 doi: 10.1158/1078-0432.CCR-20-4256
Lee, A. H. et al. Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma. Nat. Commun. 12, 6938 (2021).
pubmed: 34836966 pmcid: 8626557 doi: 10.1038/s41467-021-26940-2
Zhang, X. et al. IDH mutant gliomas escape natural killer cell immune surveillance by downregulation of NKG2D ligand expression. Neuro. Oncol. 18, 1402–1412 (2016).
pubmed: 27116977 pmcid: 5035522 doi: 10.1093/neuonc/now061
Chen, Y.-A. et al. Extrachromosomal telomere repeat DNA is linked to ALT development via cGAS-STING DNA sensing pathway. Nat. Struct. Mol. Biol. 24, 1124–1131 (2017).
pubmed: 29106411 doi: 10.1038/nsmb.3498
Wan, D., Jiang, W. & Hao, J. Research advances in how the cGAS-STING pathway controls the cellular inflammatory response. Front Immunol. 11, 615 (2020).
pubmed: 32411126 pmcid: 7198750 doi: 10.3389/fimmu.2020.00615
Floyd, W. et al. Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus. J. Clin. Invest. 133, e149310 (2023).
pubmed: 37200088 pmcid: 10313374 doi: 10.1172/JCI149310
Zheng, J. et al. RIG-I-like receptors: molecular mechanism of activation and signaling. Adv. Immunol. 158, 1–74 (2023).
pubmed: 37453753 doi: 10.1016/bs.ai.2023.03.001
Sadic, D. et al. Atrx promotes heterochromatin formation at retrotransposons. EMBO Rep. 16, 836–850 (2015).
pubmed: 26012739 pmcid: 4515123 doi: 10.15252/embr.201439937
Valenzuela, M., Amato, R., Sgura, A., Antoccia, A. & Berardinelli, F. The multiple facets of ATRX protein. Cancers (Basel) 13, 2211 (2021).
pubmed: 34062956 doi: 10.3390/cancers13092211
Chiappinelli, K. B. et al. Inhibiting DNA methylation causes an interferon response in cancer via dsrna including endogenous retroviruses. Cell 162, 974–986 (2015).
pubmed: 26317466 pmcid: 4556003 doi: 10.1016/j.cell.2015.07.011
Canadas, I. et al. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat. Med. 24, 1143–1150 (2018).
pubmed: 30038220 pmcid: 6082722 doi: 10.1038/s41591-018-0116-5
Roulois, D. et al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162, 961–973 (2015).
pubmed: 26317465 pmcid: 4843502 doi: 10.1016/j.cell.2015.07.056
Johnson, B. E. et al. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 343, 189–193 (2014).
pubmed: 24336570 doi: 10.1126/science.1239947
Ohba, S. et al. Mutant IDH1 expression drives TERT promoter reactivation as part of the cellular transformation process. Cancer Res. 76, 6680–6689 (2016).
pubmed: 27758882 pmcid: 5290072 doi: 10.1158/0008-5472.CAN-16-0696
Szatmari, T. et al. Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy. Cancer Sci. 97, 546–553 (2006).
pubmed: 16734735 doi: 10.1111/j.1349-7006.2006.00208.x
Wang, Y. et al. G-quadruplex DNA drives genomic instability and represents a targetable molecular abnormality in ATRX-deficient malignant glioma. Nat. Commun. 10, 1–14 (2019).
Struys, E. A., Jansen, E. E., Verhoeven, N. M. & Jakobs, C. Measurement of urinary D- and L-2-hydroxyglutarate enantiomers by stable-isotope-dilution liquid chromatography-tandem mass spectrometry after derivatization with diacetyl-L-tartaric anhydride. Clin. Chem. 50, 1391–1395 (2004).
pubmed: 15166110 doi: 10.1373/clinchem.2004.033399
Pirozzi, C. J. et al. Mutant IDH1 disrupts the mouse subventricular zone and alters brain tumor progression. Mol. Cancer Res. 15, 507–520 (2017).
pubmed: 28148827 pmcid: 5415422 doi: 10.1158/1541-7786.MCR-16-0485
Waitkus, M. S. et al. Adaptive evolution of the GDH2 allosteric domain promotes gliomagenesis by resolving IDH1(R132H)-induced metabolic liabilities. Cancer Res. 78, 36–50 (2018).
pubmed: 29097607 doi: 10.1158/0008-5472.CAN-17-1352

Auteurs

Seethalakshmi 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.

Benjamin T Whitfield (BT)

Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Christopher J 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.

Matthew S 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.

Michael C 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.

Michelle L 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.

David M Irvin (DM)

Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Kristen 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.

Rebecca 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.

Janell 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.

Sharvari Dharmaiah (S)

Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Emiley A 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.

Aaron 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.

Avani 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.

Casey 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.

Mariah 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.

Kevin 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.

Gao 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.

Prit Benny Malgulwar (PB)

Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Hannah Roberts (H)

Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Martin 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.

Ivan 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.

Stephen T 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.

Yiping 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.

Maria G Castro (MG)

Department of Neurosurgery, University of Michigan Medical Center, Ann Arbor, MI, USA.

Jason T Huse (JT)

Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. jhuse@mdanderson.org.

David M 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.

Classifications MeSH