{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:57:55Z","timestamp":1787497075810,"version":"build-2736575974"},"reference-count":79,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>World Health Organization (WHO) grade 4 gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade gliomas (sHGG), cerebellar high-grade gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade astrocytoma with piloid features (HGAP, ~31% of tumors); (2) H3K27M diffuse midline glioma (~8%); and (3) isocitrate dehydrogenase (IDH) wildtype glioblastoma (~43%). The latter had an unusually low-frequency of epidermal growth factor receptor (EGFR) and high-frequency of platelet-derived growth factor receptor alpha (PDGFRA) amplification, reflecting a different composition of methylation classes compared to supratentorial IDH-wildtype tumors. These new classifications have begun to reveal insights into the pathogenesis of HGG in the cerebellum and lead toward individualized treatment targeted toward the appropriate subclass of cHGG. Emerging therapeutic strategies include targeting the mitogen-activated protein kinases (MAPK) pathway and PDGFRA, oncolytic virotherapy, and immunotherapy. HGGs of the cerebellum exhibit biological differences compared to sHGG, and improved understanding of their molecular subclasses has the potential to advance treatment.<\/jats:p>","DOI":"10.3390\/cancers15010174","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T05:30:27Z","timestamp":1672205427000},"page":"174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cerebellar High-Grade Glioma: A Translationally Oriented Review of the Literature"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-3833","authenticated-orcid":false,"given":"Ashley L. B.","family":"Raghu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Oxford Functional Neurosurgery Group, Nuffield Departments of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Neurosurgery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo A.","family":"Valdes","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4640-0563","authenticated-orcid":false,"given":"Walid Ibn","family":"Essayed","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Neurosurgery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Claus","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Arnaout","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Antonio","family":"Chiocca","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo","family":"Peruzzi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7814-3867","authenticated-orcid":false,"given":"Joshua D.","family":"Bernstock","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Neurosurgery, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.1016\/j.wneu.2013.02.010","article-title":"Adult Cerebellar Glioblastoma: Understanding Survival and Prognostic Factors Using a Population-Based Database from 1973 to 2009","volume":"80","author":"Adams","year":"2013","journal-title":"World Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1002\/cne.24040","article-title":"The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting: Quantifying neurons and glia in human brain","volume":"524","author":"Bahney","year":"2016","journal-title":"J. Comp. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Z\u00fclch, K.J. (1957). Brain Tumors: Their Biology and Pathology, Springer Pub. Co.","DOI":"10.1007\/978-1-4899-6571-4"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1227\/01.neu.0000430288.85680.37","article-title":"Comparison of Survival Between Cerebellar and Supratentorial Glioblastoma Patients: Surveillance, Epidemiology, and End Results (SEER) Analysis","volume":"73","author":"Jeswani","year":"2013","journal-title":"Neurosurgery"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s11060-017-2682-7","article-title":"Characteristics of cerebellar glioblastomas in adults","volume":"136","author":"Picart","year":"2018","journal-title":"J. Neurooncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ijrobp.2006.04.035","article-title":"Outcome and prognostic factors in cerebellar glioblastoma multiforme in adults: A retrospective study from the Rare Cancer Network","volume":"66","author":"Weber","year":"2006","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1023\/A:1005704006244","article-title":"Malignant gliomas of the cerebellum: An analytic review","volume":"36","author":"Djalilian","year":"1998","journal-title":"J. Neurooncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3109\/00207454.2013.791292","article-title":"Cerebellar glioblastoma multiforme: A retrospective study of 28 patients at a single institution","volume":"123","author":"Yang","year":"2013","journal-title":"Int. J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.jocn.2012.12.006","article-title":"Outcome and prognostic factors in adult cerebellar glioblastoma","volume":"20","author":"Babu","year":"2013","journal-title":"J. Clin. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/neuonc\/noy123","article-title":"Distinct genomic profile and specific targeted drug responses in adult cerebellar glioblastoma","volume":"21","author":"Cho","year":"2019","journal-title":"Neuro-Oncology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s12094-009-0379-x","article-title":"Why cerebellar glioblastoma is rare and how that indicates adjunctive use of the FDA-approved anti-emetic aprepitant might retard cerebral glioblastoma growth: A new hypothesis to an old question","volume":"11","author":"Kast","year":"2009","journal-title":"Clin. Transl. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1007\/s00701-018-3673-y","article-title":"Cerebellar glioblastoma: A clinical series with contemporary molecular analysis","volume":"160","author":"Hong","year":"2018","journal-title":"Acta Neurochir."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6002","DOI":"10.1158\/1078-0432.CCR-09-0715","article-title":"IDH1 Mutations as Molecular Signature and Predictive Factor of Secondary Glioblastomas","volume":"15","author":"Nobusawa","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1750-3639.1996.tb00848.x","article-title":"Overexpression of the EGF Receptor and p53 Mutations are Mutually Exclusive in the Evolution of Primary and Secondary Glioblastomas","volume":"6","author":"Watanabe","year":"1996","journal-title":"Brain Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1056\/NEJMoa0808710","article-title":"IDH1 and IDH2 Mutations in Gliomas","volume":"360","author":"Yan","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.yexmp.2014.07.009","article-title":"The impact of TP53 and RAS mutations on cerebellar glioblastomas","volume":"97","author":"Milinkovic","year":"2014","journal-title":"Exp. Mol. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ccr.2009.12.020","article-title":"Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1","volume":"17","author":"Verhaak","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.cell.2013.09.034","article-title":"The Somatic Genomic Landscape of Glioblastoma","volume":"155","author":"Brennan","year":"2013","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10014-011-0070-0","article-title":"Adult cerebellar glioblastoma cases have different characteristics from supratentorial glioblastoma","volume":"29","author":"Utsuki","year":"2012","journal-title":"Brain Tumor Pathol."},{"key":"ref_20","first-page":"1351","article-title":"Prognosis of Cerebellar Glioblastomas: Correlation Between Prognosis and Immunoreactivity for Epidermal Growth Factor Receptor Compared with Supratentorial Glioblastomas","volume":"26","author":"Saito","year":"2006","journal-title":"Anticancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.3892\/mmr.2014.2549","article-title":"Clinical characteristics and pathogenesis of cerebellar glioblastoma","volume":"10","author":"Takahashi","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ccr.2012.08.024","article-title":"Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma","volume":"22","author":"Sturm","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"vdaa142","DOI":"10.1093\/noajnl\/vdaa142","article-title":"Clinical, radiologic, and genetic characteristics of histone H3 K27M-mutant diffuse midline gliomas in adults","volume":"2","author":"Schulte","year":"2020","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s40478-019-0801-8","article-title":"Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities","volume":"7","author":"Reinhardt","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s00401-017-1771-1","article-title":"Distinct molecular profile of diffuse cerebellar gliomas","volume":"134","author":"Nomura","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11060-021-03749-z","article-title":"High-grade astrocytoma with piloid features (HGAP): The Charit\u00e9 experience with a new central nervous system tumor entity","volume":"153","author":"Bender","year":"2021","journal-title":"J. Neurooncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00401-018-1837-8","article-title":"Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A\/B and ATRX alterations","volume":"136","author":"Reinhardt","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s11060-011-0617-2","article-title":"Cerebellar glioblastoma: A retrospective review of 21 patients at a single institution","volume":"105","author":"Tsung","year":"2011","journal-title":"J. Neurooncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/0360-3016(81)90189-9","article-title":"Primary malignant cerebellar astrocytomas in children: A signal for postoperative craniospinal irradiation","volume":"7","author":"Salazar","year":"1981","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0360-3016(01)01609-1","article-title":"EGFR overexpression and radiation response in glioblastoma multiforme","volume":"51","author":"Barker","year":"2001","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/0360-3016(95)02184-1","article-title":"Epidermal growth factor receptor: An independent predictor of survival in astrocytic tumors given definitive irradiation","volume":"34","author":"Zhu","year":"1996","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/ng.2682","article-title":"Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma","volume":"45","author":"Jones","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1097\/NEN.0000000000000226","article-title":"BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum","volume":"74","author":"Faulkner","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1200\/JCO.2014.58.3922","article-title":"BRAF Mutation and CDKN2A Deletion Define a Clinically Distinct Subgroup of Childhood Secondary High-Grade Glioma","volume":"33","author":"Mistry","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"59","DOI":"10.5414\/NP301105","article-title":"ATRX protein loss and deregulation of PI3K\/AKT pathway is frequent in pilocytic astrocytoma with anaplastic features","volume":"38","author":"Olar","year":"2019","journal-title":"Clin. Neuropathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.1073\/pnas.1219232110","article-title":"Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas","volume":"110","author":"Sievert","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"84697","DOI":"10.18632\/oncotarget.20949","article-title":"Overcoming resistance to single-agent therapy for oncogenic BRAF gene fusions via combinatorial targeting of MAPK and PI3K\/mTOR signaling pathways","volume":"8","author":"Jain","year":"2017","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1093\/neuonc\/nox044","article-title":"Combination therapy with potent PI3K and MAPK inhibitors overcomes adaptive kinome resistance to single agents in preclinical models of glioblastoma","volume":"19","author":"McNeill","year":"2017","journal-title":"Neuro-Oncology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s11060-009-9885-5","article-title":"Glioblastoma cell growth is suppressed by disruption of fibroblast growth factor pathway signaling","volume":"94","author":"Loilome","year":"2009","journal-title":"J. Neurooncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"328ra28","DOI":"10.1126\/scitranslmed.aac8228","article-title":"ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma","volume":"8","author":"Koschmann","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1126\/science.1257216","article-title":"Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors","volume":"347","author":"Flynn","year":"2015","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"55319","DOI":"10.18632\/oncotarget.19429","article-title":"CDK4\/6 inhibition is more active against the glioblastoma proneural subtype","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s11060-018-2977-3","article-title":"Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma","volume":"140","author":"Taylor","year":"2018","journal-title":"J. Neurooncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17033","DOI":"10.1038\/cddiscovery.2017.33","article-title":"Combination of palbociclib and radiotherapy for glioblastoma","volume":"3","author":"Whittaker","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_46","first-page":"1519","article-title":"Inhibition of DNA damage repair by the CDK4\/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth","volume":"18","author":"Hashizume","year":"2016","journal-title":"Neuro-Oncology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nm.3855","article-title":"Functionally defined therapeutic targets in diffuse intrinsic pontine glioma","volume":"21","author":"Grasso","year":"2015","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e1328340","DOI":"10.1080\/2162402X.2017.1328340","article-title":"K27M-mutant histone-3 as a novel target for glioma immunotherapy","volume":"6","author":"Ochs","year":"2017","journal-title":"OncoImmunology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41586-022-04489-4","article-title":"GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas","volume":"603","author":"Majzner","year":"2022","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41591-018-0006-x","article-title":"Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas","volume":"24","author":"Mount","year":"2018","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1093\/neuonc\/noac093","article-title":"STAT3 is a biologically relevant therapeutic target in H3K27M-mutant diffuse midline glioma","volume":"24","author":"Zhang","year":"2022","journal-title":"Neuro-Oncology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e17040","DOI":"10.1038\/sigtrans.2017.40","article-title":"Targeting cellular pathways in glioblastoma multiforme","volume":"2","author":"Pearson","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"676301","DOI":"10.3389\/fimmu.2021.676301","article-title":"Immunotherapy for Glioblastoma: Current Progress and Challenges","volume":"12","author":"Yu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41571-018-0003-5","article-title":"Current state of immunotherapy for glioblastoma","volume":"15","author":"Lim","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"Patel","year":"2014","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4009","DOI":"10.1073\/pnas.1219747110","article-title":"Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics","volume":"110","author":"Sottoriva","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1038\/s41591-018-0086-7","article-title":"Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells","volume":"24","author":"Vinci","year":"2018","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"582106","DOI":"10.3389\/fimmu.2020.582106","article-title":"Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment","volume":"11","author":"Pearson","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bernstock, J.D., Hoffman, S.E., Chen, J.A., Gupta, S., Kappel, A.D., Smith, T.R., and Chiocca, E.A. (2021). The Current Landscape of Oncolytic Herpes Simplex Viruses as Novel Therapies for Brain Malignancies. Viruses, 13.","DOI":"10.3390\/v13061158"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Uche, I.K., Kousoulas, K.G., and Rider, P.J.F. (2021). The Effect of Herpes Simplex Virus-Type-1 (HSV-1) Oncolytic Immunotherapy on the Tumor Microenvironment. Viruses, 13.","DOI":"10.3390\/v13071200"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41417-019-0091-0","article-title":"Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice","volume":"27","author":"Bernstock","year":"2020","journal-title":"Cancer Gene Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1056\/NEJMoa2024947","article-title":"Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas","volume":"384","author":"Friedman","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1089\/hum.2020.101","article-title":"Design and Rationale for First-in-Human Phase 1 Immunovirotherapy Clinical Trial of Oncolytic HSV G207 to Treat Malignant Pediatric Cerebellar Brain Tumors","volume":"31","author":"Bernstock","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1001\/jamaoncol.2020.1024","article-title":"Effect of Nivolumab vs Bevacizumab in Patients with Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial","volume":"6","author":"Reardon","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11912-020-01007-5","article-title":"Current Advances in Immunotherapy for Glioblastoma","volume":"23","author":"Mende","year":"2021","journal-title":"Curr. Oncol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41591-018-0337-7","article-title":"Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma","volume":"25","author":"Cloughesy","year":"2019","journal-title":"Nat. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0191-1","article-title":"Immune checkpoint inhibitors: Recent progress and potential biomarkers","volume":"50","author":"Darvin","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"91779","DOI":"10.18632\/oncotarget.21586","article-title":"Recurrent glioma clinical trial, CheckMate-143: The game is not over yet","volume":"8","author":"Filley","year":"2017","journal-title":"Oncotarget"},{"key":"ref_69","first-page":"493","article-title":"Immunovirotherapy with measles virus strains in combination with anti\u2013PD-1 antibody blockade enhances antitumor activity in glioblastoma treatment","volume":"19","author":"Hardcastle","year":"2016","journal-title":"Neuro-Oncology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ccell.2017.07.006","article-title":"Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade","volume":"32","author":"Saha","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12967-018-1507-6","article-title":"First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma","volume":"16","author":"Liau","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3171\/jns.1979.50.3.0305","article-title":"Macrophages in experimental and human brain tumors","volume":"50","author":"Morantz","year":"1979","journal-title":"J. Neurosurg."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nn.4185","article-title":"The role of microglia and macrophages in glioma maintenance and progression","volume":"19","author":"Hambardzumyan","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/s41568-021-00397-3","article-title":"Glial and myeloid heterogeneity in the brain tumour microenvironment","volume":"21","author":"Andersen","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/nm.3337","article-title":"CSF-1R inhibition alters macrophage polarization and blocks glioma progression","volume":"19","author":"Pyonteck","year":"2013","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"aad3018","DOI":"10.1126\/science.aad3018","article-title":"The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas","volume":"352","author":"Quail","year":"2016","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/neuonc\/nov245","article-title":"Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: An Ivy Foundation Early Phase Clinical Trials Consortium phase II study","volume":"18","author":"Butowski","year":"2016","journal-title":"Neuro-Oncology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"103453","DOI":"10.1016\/j.ebiom.2021.103453","article-title":"Current knowledge on the immune microenvironment and emerging immunotherapies in diffuse midline glioma","volume":"69","author":"Price","year":"2021","journal-title":"eBioMedicine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ccell.2017.06.003","article-title":"Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment","volume":"32","author":"Wang","year":"2017","journal-title":"Cancer Cell"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/1\/174\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:53:31Z","timestamp":1760147611000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/1\/174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,28]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["cancers15010174"],"URL":"https:\/\/doi.org\/10.3390\/cancers15010174","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,28]]}}}