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Of the 14 currently recognized and described cancer hallmarks, five are especially implicated in malignant glioma and targetable with repurposed drugs: cancer stem-like cells, in general, and glioma stem-like cells in particular (GSCs), vascularization and hypoxia, metabolic reprogramming, tumor-promoting inflammation and sustained proliferative signaling. Each hallmark drives malignant glioma development, both individually and through interactions with other hallmarks, in which the TME plays a critical role. To combat the aggressive malignant glioma spatio-temporal heterogeneity driven by TME interactions, and to overcome its therapeutic challenges, a combined treatment strategy including anticancer therapies, repurposed drugs and multimodal immunotherapy should be the aim for future treatment approaches.<\/jats:p>","DOI":"10.3390\/cancers17050879","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T05:41:51Z","timestamp":1741066911000},"page":"879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Complexity of Malignant Glioma Treatment"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3479-3593","authenticated-orcid":false,"given":"Linde F. 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(2022). Managing the TME to improve the efficacy of cancer therapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.954992"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1470-2045(09)70025-7","article-title":"Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial","volume":"10","author":"Stupp","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1038\/s41388-023-02738-y","article-title":"Glioblastoma heterogeneity at single cell resolution","volume":"42","author":"Eisenbarth","year":"2023","journal-title":"Oncogene"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Suter, R.K., Rodriguez-Blanco, J., and Ayad, N.G. (2020). Epigenetic pathways and plasticity in brain tumors. Neurobiol. Dis., 145.","DOI":"10.1016\/j.nbd.2020.105060"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41568-022-00475-0","article-title":"Disconnecting multicellular networks in brain tumours","volume":"22","author":"Venkataramani","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nature16071","article-title":"Brain tumour cells interconnect to a functional and resistant network","volume":"528","author":"Osswald","year":"2015","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pericoli, G., Galardi, A., Paolini, A., Petrilli, L.L., Pepe, G., Palma, A., Colletti, M., Ferretti, R., Giorda, E., and Levi Mortera, S. (2023). Inhibition of exosome biogenesis affects cell motility in heterogeneous sub-populations of paediatric-type diffuse high-grade gliomas. Cell Biosci., 13.","DOI":"10.1186\/s13578-023-01166-5"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/s41586-023-06678-1","article-title":"Glioma synapses recruit mechanisms of adaptive plasticity","volume":"623","author":"Taylor","year":"2023","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/s41586-019-1564-x","article-title":"Glutamatergic synaptic input to glioma cells drives brain tumour progression","volume":"573","author":"Venkataramani","year":"2019","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nature24014","article-title":"Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma","volume":"549","author":"Venkatesh","year":"2017","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e30813","DOI":"10.1016\/j.heliyon.2024.e30813","article-title":"Non-targeted effects of radiation therapy for glioblastoma","volume":"10","author":"Lerouge","year":"2024","journal-title":"Heliyon"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Van Gool, S.W., Makalowski, J., Fiore, S., Sprenger, T., Prix, L., Schirrmacher, V., and Stuecker, W. (2021). Randomized Controlled Immunotherapy Clinical Trials for GBM Challenged. Cancers, 13.","DOI":"10.3390\/cancers13010032"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhao, R., Pan, Z., Li, B., Zhao, S., Zhang, S., Qi, Y., Qiu, J., Gao, Z., Fan, Y., and Guo, Q. (2022). Comprehensive Analysis of the Tumor Immune Microenvironment Landscape in Glioblastoma Reveals Tumor Heterogeneity and Implications for Prognosis and Immunotherapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.820673"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tanner, G., Barrow, R., Ajaib, S., Al-Jabri, M., Ahmed, N., Pollock, S., Finetti, M., Rippaus, N., Bruns, A.F., and Syed, K. (2024). IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy. Genome Biol., 25.","DOI":"10.1186\/s13059-024-03172-3"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"De Simone, M., Iaconetta, G., Palermo, G., Fiorindi, A., Schaller, K., and De Maria, L. (2024). Clustering Functional Magnetic Resonance Imaging Time Series in Glioblastoma Characterization: A Review of the Evolution, Applications, and Potentials. Brain Sci., 14.","DOI":"10.3390\/brainsci14030296"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Becker, A.P., Sells, B.E., Haque, S.J., and Chakravarti, A. (2021). Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology. Cancers, 13.","DOI":"10.3390\/cancers13040761"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6870","DOI":"10.1038\/s41467-024-51315-8","article-title":"A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine","volume":"15","author":"Latzer","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Karimi-Sani, I., Molavi, Z., Naderi, S., Mirmajidi, S.-H., Zare, I., Naeimzadeh, Y., Mansouri, A., Tajbakhsh, A., Savardashtaki, A., and Sahebkar, A. (2024). Personalized mRNA vaccines in glioblastoma therapy: From rational design to clinical trials. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02882-x"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Van Gool, S.W., Makalowski, J., Van de Vliet, P., Van Gool, S., Sprenger, T., Schirrmacher, V., and Stuecker, W. (2023). Individualized Multimodal Immunotherapy for Adults with IDH1 Wild-Type GBM: A Single Institute Experience. Cancers, 15.","DOI":"10.3390\/cancers15041194"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1002\/cam4.2192","article-title":"Immune microenvironments differ in immune characteristics and outcome of glioblastoma multiforme","volume":"8","author":"Zhang","year":"2019","journal-title":"Cancer Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Garnier, D., Renoult, O., Alves-Guerra, M.-C., Paris, F., and Pecqueur, C. (2019). Glioblastoma Stem-Like Cells, Metabolic Strategy to Kill a Challenging Target. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00118"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shi, T., Zhu, J., Zhang, X., and Mao, X. (2023). The Role of Hypoxia and Cancer Stem Cells in Development of Glioblastoma. Cancers, 15.","DOI":"10.3390\/cancers15092613"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1038\/s41467-020-17186-5","article-title":"Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy","volume":"11","author":"Couturier","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10747","DOI":"10.1111\/jcmm.17016","article-title":"Clinically relevant preservation conditions for mesenchymal stem\/stromal cells derived from perinatal and adult tissue sources","volume":"25","author":"Ngo","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1158\/2159-8290.CD-14-0471","article-title":"Brain Tumor Cells in Circulation Are Enriched for Mesenchymal Gene Expression","volume":"4","author":"Sullivan","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1093\/neuonc\/noac085","article-title":"Glioblastoma scRNA-seq shows treatment-induced, immune-dependent increase in mesenchymal cancer cells and structural variants in distal neural stem cells","volume":"24","author":"Couturier","year":"2022","journal-title":"Neuro-Oncology"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Park, J.H., Pyun, W.Y., and Park, H.W. (2020). Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets. Cells, 9.","DOI":"10.3390\/cells9102308"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Majc, B., Sever, T., Zari\u0107, M., Breznik, B., Turk, B., and Lah, T.T. (2020). Epithelial-to-mesenchymal transition as the driver of changing carcinoma and glioblastoma microenvironment. Biochim. Biophys. Acta BBA\u2014Mol. Cell Res., 1867.","DOI":"10.1016\/j.bbamcr.2020.118782"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, X., Liang, J., and Sun, H. (2022). The Network of Tumor Microtubes: An Improperly Reactivated Neural Cell Network With Stemness Feature for Resistance and Recurrence in Gliomas. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.921975"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s00280-017-3329-2","article-title":"Reversing glioma malignancy: A new look at the role of antidepressant drugs as adjuvant therapy for glioblastoma multiforme","volume":"79","author":"Lesiak","year":"2017","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"435","DOI":"10.2174\/156652409788167122","article-title":"Novel Imaging Provides New Insights into Mechanisms of Oxygen Transport in Tumors","volume":"9","author":"Hardee","year":"2009","journal-title":"Curr. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1158\/0008-5472.CAN-03-2958","article-title":"Direct Demonstration of Instabilities in Oxygen Concentrations within the Extravascular Compartment of an Experimental Tumor","volume":"66","author":"Lanzen","year":"2006","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5812","DOI":"10.1158\/0008-5472.CAN-07-6387","article-title":"The Pervasive Presence of Fluctuating Oxygenation in Tumors","volume":"68","author":"Mace","year":"2008","journal-title":"Cancer Res."},{"key":"ref_41","first-page":"76","article-title":"Cycling hypoxia: A key feature of the tumor microenvironment","volume":"1866","author":"Michiels","year":"2016","journal-title":"Biochim. Biophys. Acta BBA\u2014Rev. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Saxena, K., and Jolly, M.K. (2019). Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression. Biomolecules, 9.","DOI":"10.3390\/biom9080339"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lavogina, D., Kr\u00f5lov, M.K., Vellama, H., Modhukur, V., Di Nisio, V., Lust, H., Eskla, K.-L., Salumets, A., and Jaal, J. (2024). Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-54707-4"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lo Dico, A., Martelli, C., Diceglie, C., Lucignani, G., and Ottobrini, L. (2018). Hypoxia-Inducible Factor-1\u03b1 Activity as a Switch for Glioblastoma Responsiveness to Temozolomide. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00249"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/ars.2013.5595","article-title":"Antihelminthic Benzimidazoles Are Novel HIF Activators That Prevent Oxidative Neuronal Death via Binding to Tubulin","volume":"22","author":"Aleyasin","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"337","DOI":"10.7326\/0003-4819-144-5-200603070-00008","article-title":"Adding Chloroquine to Conventional Treatment for Glioblastoma Multiforme","volume":"144","author":"Sotelo","year":"2006","journal-title":"Ann. Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Putta, C.L., Eswar, K., and Rengan, A.K. (2023). Melatonin: Avenues in cancer therapy and its nanotechnological advancements. MedComm\u2014Biomater. Appl., 2.","DOI":"10.1002\/mba2.58"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wang, L., Wang, C., and Choi, W.S. (2022). Use of Melatonin in Cancer Treatment: Where Are We?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073779"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101617","DOI":"10.1016\/j.tice.2021.101617","article-title":"The role of melatonin in angio-miR-associated inhibition of tumorigenesis and invasion in human glioblastoma tumour spheroids","volume":"73","author":"Delen","year":"2021","journal-title":"Tissue Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1158\/1078-0432.CCR-20-2500","article-title":"Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma","volume":"27","author":"Nayak","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1016\/j.cell.2024.07.030","article-title":"Macrophage-mediated myelin recycling fuels brain cancer malignancy","volume":"187","author":"Kloosterman","year":"2024","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhou, W., and Wahl, D.R. (2019). Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance. Cancers, 11.","DOI":"10.3390\/cancers11091231"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1085\/jgp.8.6.519","article-title":"The Metabolism of Tumors in the Body","volume":"8","author":"Warburg","year":"1927","journal-title":"J. Gen. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s42255-020-0172-2","article-title":"We need to talk about the Warburg effect","volume":"2","author":"DeBerardinis","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.mehy.2010.10.037","article-title":"Necroptosis: A novel therapeutic target for glioblastoma","volume":"76","author":"Jiang","year":"2011","journal-title":"Med. Hypotheses"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5424","DOI":"10.1038\/s41467-020-19193-y","article-title":"Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression","volume":"11","author":"Yee","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ahn, S.-H., Park, H., Ahn, Y.-H., Kim, S., Cho, M.-S., Kang, J.L., and Choi, Y.-H. (2016). Necrotic cells influence migration and invasion of glioblastoma via NF-\u03baB\/AP-1-mediated IL-8 regulation. Sci. Rep., 6.","DOI":"10.1038\/srep24552"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Di Ianni, N., Musio, S., and Pellegatta, S. (2021). Altered Metabolism in Glioblastoma: Myeloid-Derived Suppressor Cell (MDSC) Fitness and Tumor-Infiltrating Lymphocyte (TIL) Dysfunction. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094460"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Mahalingam, D., Goel, S., Aparo, S., Patel Arora, S., Noronha, N., Tran, H., Chakrabarty, R., Selvaggi, G., Gutierrez, A., and Coffey, M. (2018). A Phase II Study of Pelareorep (REOLYSIN\u00ae) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma. Cancers, 10.","DOI":"10.3390\/cancers10060160"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e37792","DOI":"10.1016\/j.heliyon.2024.e37792","article-title":"Metformin impacts the differentiation of mouse bone marrow cells into macrophages affecting tumour immunity","volume":"10","author":"Scafidi","year":"2024","journal-title":"Heliyon"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"33440","DOI":"10.18632\/oncotarget.7961","article-title":"PI3K\/Akt\/mTOR signaling pathway and targeted therapy for glioblastoma","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhao, L., Zhang, H., Zhang, Y., Ju, H., Wang, X., Ren, H., Zhu, X., and Dong, Y. (2022). The immunosuppressive microenvironment and immunotherapy in human glioblastoma. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1003651"},{"key":"ref_63","first-page":"1111","article-title":"TGF-\u03b2 links glycolysis and immunosuppression in glioblastoma","volume":"36","author":"Gong","year":"2021","journal-title":"Histol. Histopathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1093\/brain\/aww355","article-title":"Glioblastoma-associated microglia and macrophages: Targets for therapies to improve prognosis","volume":"140","author":"Poon","year":"2017","journal-title":"Brain"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Geribaldi-Dold\u00e1n, N., Fern\u00e1ndez-Ponce, C., Quiroz, R.N., S\u00e1nchez-Gomar, I., Escorcia, L.G., Vel\u00e1squez, E.P., and Quiroz, E.N. (2021). The Role of Microglia in Glioblastoma. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.603495"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Pace, A., Scirocchi, F., Napoletano, C., Zizzari, I.G., D\u2019Angelo, L., Santoro, A., Nuti, M., Rahimi, H., and Rughetti, A. (2022). Glycan-Lectin Interactions as Novel Immunosuppression Drivers in Glioblastoma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116312"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4239","DOI":"10.1038\/s41388-018-0261-9","article-title":"Immunosuppressive effects of hypoxia-induced glioma exosomes through myeloid-derived suppressor cells via the miR-10a\/Rora and miR-21\/Pten Pathways","volume":"37","author":"Guo","year":"2018","journal-title":"Oncogene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/cas.13244","article-title":"M2-like macrophage polarization in high lactic acid-producing head and neck cancer","volume":"108","author":"Ohashi","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.immuni.2024.04.006","article-title":"Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma","volume":"57","author":"Leo","year":"2024","journal-title":"Immunity"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hao, Z.-N., Tan, X.-P., Zhang, Q., Li, J., Xia, R., and Ma, Z. (2024). Lactate and Lactylation: Dual Regulators of T-Cell-Mediated Tumor Immunity and Immunotherapy. Biomolecules, 14.","DOI":"10.3390\/biom14121646"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e130748","DOI":"10.1172\/jci.insight.130748","article-title":"Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells","volume":"4","author":"Peereboom","year":"2019","journal-title":"JCI Insight"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Yanchu, L., Rong, P., Rong, C., Li, Z., Xiaoyan, Y., and Feng, W. (2023). Ozone therapy for high-grade glioma: An overview. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1161206"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e163446","DOI":"10.1172\/JCI163446","article-title":"Macrophages and microglia in glioblastoma: Heterogeneity, plasticity, and therapy","volume":"133","author":"Khan","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11060-020-03483-y","article-title":"Immune suppression in gliomas","volume":"151","author":"Grabowski","year":"2021","journal-title":"J. Neurooncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00018.2019","article-title":"Immunity, Hypoxia, and Metabolism\u2013the M\u00e9nage \u00e0 Trois of Cancer: Implications for Immunotherapy","volume":"100","author":"Granja","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1016\/j.cell.2020.04.055","article-title":"Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes","volume":"181","author":"Friebel","year":"2020","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Messiaen, J., Jacobs, S.A., and De Smet, F. (2023). The tumor micro-environment in pediatric glioma: Friend or foe?. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1227126"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Paul, S., and Sa, G. (2021). Curcumin as an Adjuvant to Cancer Immunotherapy. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.675923"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Exley, M.A., Garcia, S., Zellander, A., Zilberberg, J., and Andrews, D.W. (2022). Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma. J. Clin. Med., 11.","DOI":"10.3390\/jcm11041069"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ccell.2021.11.002","article-title":"The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1","volume":"40","author":"Li","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"101246","DOI":"10.1016\/j.xcrm.2023.101246","article-title":"Microglia in pediatric brain tumors: The missing link to successful immunotherapy","volume":"4","author":"Velilla","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1016\/j.immuni.2024.09.007","article-title":"Microglia and monocyte-derived macrophages drive progression of pediatric high-grade gliomas and are transcriptionally shaped by histone mutations","volume":"57","author":"Ross","year":"2024","journal-title":"Immunity"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"101377","DOI":"10.1016\/j.xcrm.2023.101377","article-title":"Lymph node and tumor-associated PD-L1+ macrophages antagonize dendritic cell vaccines by suppressing CD8+ T cells","volume":"5","author":"Sprooten","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1038\/s41467-020-17670-y","article-title":"A decade of immune-checkpoint inhibitors in cancer therapy","volume":"11","author":"Robert","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"57932","DOI":"10.18632\/oncotarget.10773","article-title":"Anti-cancer effects of nitrogen-containing bisphosphonates on human cancer cells","volume":"7","author":"Jiang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/cmi.2012.39","article-title":"What lessons can be learned from \u03b3\u03b4 T cell-based cancer immunotherapy trials?","volume":"10","author":"Sicard","year":"2013","journal-title":"Cell. Mol. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00432-010-0873-0","article-title":"Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma","volume":"137","author":"Lins","year":"2011","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_88","first-page":"5625","article-title":"Long-term Outcome in Patients with Recurrent Malignant Glioma Treated with Perillyl Alcohol Inhalation","volume":"33","author":"Fonseca","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Heylmann, D., Bauer, M., Becker, H., van Gool, S., Bacher, N., Steinbrink, K., and Kaina, B. (2013). Human CD4+CD25+ regulatory T cells are sensitive to low dose cyclophosphamide: Implications for the immune response. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083384"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/eji.200324181","article-title":"CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative","volume":"34","author":"Ghiringhelli","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Zhong, H., Lai, Y., Zhang, R., Daoud, A., Feng, Q., Zhou, J., and Shang, J. (2020). Low Dose Cyclophosphamide Modulates Tumor Microenvironment by TGF-\u03b2 Signaling Pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030957"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Ferrer-Font, L., Arias-Ramos, N., Lope-Piedrafita, S., Juli\u00e0-Sap\u00e9, M., Pumarola, M., Ar\u00fas, C., and Candiota, A.P. (2017). Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: Effects of cyclophosphamide and temozolomide. NMR Biomed., 30.","DOI":"10.1002\/nbm.3748"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ymthe.2005.08.016","article-title":"Phase I\/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme","volume":"13","author":"Freeman","year":"2006","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Romero, N., Palac\u00edn-Aliana, I., Esteban-Rubio, S., Madurga, R., Rius-Rocabert, S., Carri\u00f3n-Navarro, J., Presa, J., Cuadrado-Castano, S., S\u00e1nchez-G\u00f3mez, P., and Garc\u00eda-Sastre, A. (2020). Newcastle Disease Virus (NDV) Oncolytic Activity in Human Glioma Tumors Is Dependent on CDKN2A-Type I IFN Gene Cluster Codeletion. Cells, 9.","DOI":"10.3390\/cells9061405"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e004644","DOI":"10.1136\/jitc-2022-004644","article-title":"Inhibition of D-2HG leads to upregulation of a proinflammatory gene signature in a novel HLA-A2\/HLA-DR1 transgenic mouse model of IDH1R132H-expressing glioma","volume":"10","author":"Chuntova","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1172\/JCI90644","article-title":"Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas","volume":"127","author":"Kohanbash","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Kaminska, B., Czapski, B., Guzik, R., Kr\u00f3l, S.K., and Gielniewski, B. (2019). Consequences of IDH1\/2 Mutations in Gliomas and an Assessment of Inhibitors Targeting Mutated IDH Proteins. Molecules, 24.","DOI":"10.3390\/molecules24050968"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-021-03363-z","article-title":"A vaccine targeting mutant IDH1 in newly diagnosed glioma","volume":"592","author":"Platten","year":"2021","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Li, W., Wang, Z., Chen, S., Zuo, M., Xiang, Y., Yuan, Y., He, Y., Zhang, S., and Liu, Y. (2024). Metabolic checkpoints in glioblastomas: Targets for new therapies and non-invasive detection. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1462424"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41392-023-01705-z","article-title":"Targeting the RAS\/RAF\/MAPK pathway for cancer therapy: From mechanism to clinical studies","volume":"8","author":"Bahar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00401-004-0936-x","article-title":"Mutation analysis of B-RAF gene in human gliomas","volume":"109","author":"Basto","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41586-019-1563-y","article-title":"Electrical and synaptic integration of glioma into neural circuits","volume":"573","author":"Venkatesh","year":"2019","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1146\/annurev-neuro-111020-092702","article-title":"Neural Signaling in Cancer","volume":"45","author":"Keough","year":"2022","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Pan, Y., and Monje, M. (2022). Neuron\u2013Glial Interactions in Health and Brain Cancer. Adv. Biol., 6.","DOI":"10.1002\/adbi.202200122"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1016\/j.cell.2022.06.054","article-title":"Glioblastoma hijacks neuronal mechanisms for brain invasion","volume":"185","author":"Venkataramani","year":"2022","journal-title":"Cell"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Barron, T., Yal\u00e7\u0131n, B., Mochizuki, A., Cantor, E., Shamardani, K., Tlais, D., Franson, A., Lyons, S., Mehta, V., and Jahan, S.M. (2022). GABAergic neuron-to-glioma synapses in diffuse midline gliomas. bioRxiv.","DOI":"10.1101\/2022.11.08.515720"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"123067","DOI":"10.1016\/j.lfs.2024.123067","article-title":"Gamma-aminobutyric acid-mediated neuro-immune interactions in glioblastoma: Implications for prognosis and immunotherapy response","volume":"357","author":"Shanyue","year":"2024","journal-title":"Life Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.ccell.2023.02.012","article-title":"Cancer hallmarks intersect with neuroscience in the tumor microenvironment","volume":"41","author":"Hanahan","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_109","first-page":"14","article-title":"Brain Tumors in Pediatric Patients","volume":"2","author":"Kumari","year":"2024","journal-title":"Int. J. Trends OncoScience"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/14737175.2018.1425617","article-title":"Immunotherapy for brain tumors: Understanding early successes and limitations","volume":"18","author":"Lieberman","year":"2018","journal-title":"Expert Rev. Neurother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Petrilli, L.L., Fuoco, C., Palma, A., Pasquini, L., Pericoli, G., Grabovska, Y., Mackay, A., Rossi, S., Carcaboso, A.M., and Carai, A. (2022). Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1016343"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4324","DOI":"10.1038\/s41467-020-18070-y","article-title":"Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity","volume":"11","author":"Grabovska","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.canrad.2024.06.003","article-title":"Overcoming the limits of pediatric brain tumor radiotherapy: The use of preclinical 3D models","volume":"28","author":"Czuba","year":"2024","journal-title":"Cancer\/Radioth\u00e9rapie"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40478-018-0553-x","article-title":"Non-inflammatory tumor microenvironment of diffuse intrinsic pontine glioma","volume":"6","author":"Lin","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/neuonc\/noy145","article-title":"Characterization of the immune microenvironment of diffuse intrinsic pontine glioma: Implications for development of immunotherapy","volume":"21","author":"Lieberman","year":"2019","journal-title":"Neuro-Oncology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/brain\/awaa382","article-title":"Platelet-derived growth factor beta is a potent inflammatory driver in paediatric high-grade glioma","volume":"144","author":"Ross","year":"2021","journal-title":"Brain"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"vdac079","DOI":"10.1093\/noajnl\/vdac079","article-title":"Generation of immunocompetent syngeneic allograft mouse models for pediatric diffuse midline glioma","volume":"4","author":"Meel","year":"2022","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.immuni.2024.11.026","article-title":"Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion","volume":"58","author":"Tomaszewski","year":"2025","journal-title":"Immunity"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Frederico, S.C., Sharma, N., Darling, C., Taori, S., Dubinsky, A.C., Zhang, X., Raphael, I., and Kohanbash, G. (2024). Myeloid cells as potential targets for immunotherapy in pediatric gliomas. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1346493"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"86","DOI":"10.14791\/btrt.2023.0011","article-title":"Epigenetic and Metabolic Changes in Diffuse Intrinsic Pontine Glioma","volume":"11","author":"Park","year":"2023","journal-title":"Brain Tumor Res. Treat."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s11060-015-1726-0","article-title":"Citrate concentrations increase with hypoperfusion in pediatric diffuse intrinsic pontine glioma","volume":"122","author":"Yeom","year":"2015","journal-title":"J. Neurooncol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Van Gool, S.W., Makalowski, J., Bonner, E.R., Feyen, O., Domogalla, M.P., Prix, L., Schirrmacher, V., Nazarian, J., and Stuecker, W. (2020). Addition of Multimodal Immunotherapy to Combination Treatment Strategies for Children with DIPG: A Single Institution Experience. Medicines, 7.","DOI":"10.3390\/medicines7050029"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1158\/2159-8290.CD-23-0131","article-title":"Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways","volume":"13","author":"Venneti","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"S136","DOI":"10.1093\/neuonc\/noad144","article-title":"A review of current therapeutics targeting the mitochondrial protease ClpP in diffuse midline glioma, H3 K27-altered","volume":"26","author":"Jackson","year":"2024","journal-title":"Neuro-Oncology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.neo.2020.09.005","article-title":"ONC201 and imipridones: Anti-cancer compounds with clinical efficacy","volume":"22","author":"Prabhu","year":"2020","journal-title":"Neoplasia"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41420-024-02011-5","article-title":"AMPK\u2013a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment?","volume":"10","author":"Wang","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.21037\/tcr-23-603","article-title":"Dendritic cell vaccination for glioblastoma multiforme patients: Has a new milestone been reached?","volume":"12","author":"Makalowski","year":"2023","journal-title":"Transl. Cancer Res."},{"key":"ref_129","first-page":"51","article-title":"Methods behind oncolytic virus-based DC vaccines in cancer: Toward a multiphase combined treatment strategy for Glioblastoma (GBM) patients","volume":"183","author":"Kampers","year":"2023","journal-title":"Methods Cell Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1001\/jama.2017.18718","article-title":"Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial","volume":"318","author":"Stupp","year":"2017","journal-title":"JAMA"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1007\/s00262-020-02534-7","article-title":"Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy","volume":"69","author":"Voloshin","year":"2020","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"33109","DOI":"10.3402\/jev.v5.33109","article-title":"Oncosomes\u2014Large and small: What are they, where they came from?","volume":"5","author":"Meehan","year":"2016","journal-title":"J. Extracell. Vesicles"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.21873\/anticanres.13315","article-title":"Immune Phenotype Correlates With Survival in Patients With GBM Treated With Standard Temozolomide-based Therapy and Immunotherapy","volume":"39","author":"Antonopoulos","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S1470-2045(17)30517-X","article-title":"Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): A randomised, double-blind, international phase 3 trial","volume":"18","author":"Weller","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3171\/JNS\/2008\/108\/5\/0963","article-title":"Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme","volume":"108","author":"Izumoto","year":"2008","journal-title":"J. Neurosurg. JNS"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"114722","DOI":"10.18632\/oncotarget.21773","article-title":"Circulating CD9+\/GFAP+\/survivin+ exosomes in malignant glioma patients following survivin vaccination","volume":"8","author":"Galbo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1038\/s41591-023-02555-6","article-title":"A H3K27M-targeted vaccine in adults with diffuse midline glioma","volume":"29","author":"Grassl","year":"2023","journal-title":"Nat. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s00262-020-02751-0","article-title":"Low-dose ipilimumab plus nivolumab combined with IL-2 and hyperthermia in cancer patients with advanced disease: Exploratory findings of a case series of 131 stage IV cancers\u2014A retrospective study of a single institution","volume":"70","author":"Kleef","year":"2021","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1200\/JCO.22.01711","article-title":"Cost Savings and Increased Access With Ultra-Low-Dose Immunotherapy","volume":"41","author":"Mitchell","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Schirrmacher, V., Van Gool, S., and Stuecker, W. (2024). Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution. Biomedicines, 12.","DOI":"10.3390\/biomedicines12040754"},{"key":"ref_141","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_142","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41577-021-00541-y","article-title":"Metabolic barriers to cancer immunotherapy","volume":"21","author":"DePeaux","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Lin, H., Yang, X., Ye, S., Huang, L., and Mu, W. (2024). Antigen escape in CAR-T cell therapy: Mechanisms and overcoming strategies. Biomed. Pharmacother., 178.","DOI":"10.1016\/j.biopha.2024.117252"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"14","DOI":"10.17305\/bjbms.2018.3532","article-title":"Cannabinoids in cancer treatment: Therapeutic potential and legislation","volume":"19","author":"Verboten","year":"2019","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1158\/0008-5472.CAN-03-3720","article-title":"Cannabinoids Induce Cancer Cell Proliferation via Tumor Necrosis Factor \u03b1-Converting Enzyme (TACE\/ADAM17)-Mediated Transactivation of the Epidermal Growth Factor Receptor","volume":"64","author":"Hart","year":"2004","journal-title":"Cancer Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41392-022-00918-y","article-title":"Cannabis suppresses antitumor immunity by inhibiting JAK\/STAT signaling in T cells through CNR2","volume":"7","author":"Xiong","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1634\/theoncologist.2018-0383","article-title":"Cannabis Impacts Tumor Response Rate to Nivolumab in Patients with Advanced Malignancies","volume":"24","author":"Taha","year":"2019","journal-title":"Oncologist"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Bar-Sela, G., Cohen, I., Campisi-Pinto, S., Lewitus, G.M., Oz-Ari, L., Jehassi, A., Peer, A., Turgeman, I., Vernicova, O., and Berman, P. (2020). Cannabis Consumption Used by Cancer Patients during Immunotherapy Correlates with Poor Clinical Outcome. Cancers, 12.","DOI":"10.3390\/cancers12092447"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"122924","DOI":"10.1016\/j.ijpharm.2023.122924","article-title":"Nucleic acid immunotherapeutics and vaccines: A promising approach to glioblastoma multiforme treatment","volume":"638","author":"Dain","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"101122","DOI":"10.1016\/j.drup.2024.101122","article-title":"Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma","volume":"76","author":"Lan","year":"2024","journal-title":"Drug Resist. Updates"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.ccell.2020.08.008","article-title":"Epigenomic Reprogramming as a Driver of Malignant Glioma","volume":"38","author":"Phillips","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s40265-024-02097-2","article-title":"Vorasidenib: First Approval","volume":"84","author":"Lamb","year":"2024","journal-title":"Drugs"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1093\/neuonc\/noae107","article-title":"The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: How should they inform treatment decisions in the era of IDH inhibitors?","volume":"26","author":"French","year":"2024","journal-title":"Neuro-Oncology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/978-981-15-8104-5_6","article-title":"Epigenetic-Targeted Treatments for H3K27M-Mutant Midline Gliomas","volume":"1283","author":"Lu","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"vdab096","DOI":"10.1093\/noajnl\/vdab096","article-title":"Inhibition of microglial EZH2 leads to anti-tumoral effects in pediatric diffuse midline gliomas","volume":"3","author":"Keane","year":"2021","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Liu, L., Huh, J.R., and Shah, K. (2022). Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS. EBioMedicine, 77.","DOI":"10.1016\/j.ebiom.2022.103908"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Zhang, H., Hong, Y., Wu, T., Ben, E., Li, S., Hu, L., and Xie, T. (2024). Role of gut microbiota in regulating immune checkpoint inhibitor therapy for glioblastoma. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1401967"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"vdac082","DOI":"10.1093\/noajnl\/vdac082","article-title":"Sexual dimorphism of the immune system predicts clinical outcomes in glioblastoma immunotherapy: A systematic review and meta-analysis","volume":"4","author":"Shireman","year":"2022","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1158\/2159-8290.CD-22-0869","article-title":"Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma","volume":"13","author":"Lee","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41698-018-0072-z","article-title":"Liquid biopsy for pediatric central nervous system tumors","volume":"2","author":"Bonner","year":"2018","journal-title":"Npj Precis. Oncol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"vdad082","DOI":"10.1093\/noajnl\/vdad082","article-title":"Spectral flow cytometry identifies distinct nonneoplastic plasma extracellular vesicle phenotype in glioblastoma patients","volume":"5","author":"Aibaidula","year":"2023","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1007\/s12094-017-1827-7","article-title":"Perspective on immune oncology with liquid biopsy, peripheral blood mononuclear cells, and microbiome with non-invasive biomarkers in cancer patients","volume":"20","author":"Mitsuhashi","year":"2018","journal-title":"Clin. Transl. Oncol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00401-018-1936-6","article-title":"Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA","volume":"137","author":"Pan","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"E8","DOI":"10.3171\/2019.9.FOCUS19712","article-title":"Liquid biopsies for the diagnosis and surveillance of primary pediatric central nervous system tumors: A review for practicing neurosurgeons","volume":"48","author":"Bounajem","year":"2020","journal-title":"Neurosurg. Focus FOC"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41416-019-0603-6","article-title":"Circulating biomarkers in patients with glioblastoma","volume":"122","author":"Kulasinghe","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Hut\u00f3czki, G., Virga, J., Birk\u00f3, Z., and Klekner, A. (2021). Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810005"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1093\/neuonc\/noab229","article-title":"Extracellular vesicles: The key for precision medicine in glioblastoma","volume":"24","author":"Osti","year":"2022","journal-title":"Neuro-Oncology"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"5850","DOI":"10.1158\/1078-0432.CCR-18-1345","article-title":"Clinically Relevant and Minimally Invasive Tumor Surveillance of Pediatric Diffuse Midline Gliomas Using Patient-Derived Liquid Biopsy","volume":"24","author":"Panditharatna","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2908609","DOI":"10.1155\/2018\/2908609","article-title":"Noninvasive Glioblastoma Testing: Multimodal Approach to Monitoring and Predicting Treatment Response","volume":"2018","author":"Verduin","year":"2018","journal-title":"Dis. Markers"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"28","DOI":"10.37349\/etat.2023.00121","article-title":"Liquid biopsy and glioblastoma","volume":"4","author":"Eibl","year":"2023","journal-title":"Explor. Target. Anti-Tumor Ther."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Malara, N., and Donato, G. (2019). Blood-Brain Barrier Breakdown by Combined Detection of Circulating Tumor and Endothelial Cells in Liquid Biopsy. Liquid Biopsy, IntechOpen.","DOI":"10.5772\/intechopen.80594"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Zaky, W., Ragoonanan, D., Batth, I., Dao, L., Wang, J., Xia, X., Daw, N.C., Gill, J.B., Khatua, S., and Li, S. (2023). Automated Capture and Analysis of Circulating Tumor Cells in Pediatric, Adolescent and Young Adult Patients with Central Nervous System Tumors. Cancers, 15.","DOI":"10.3390\/cancers15153853"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.1093\/neuonc\/noad229","article-title":"Liquid biopsy in H3K27M diffuse midline glioma","volume":"26","author":"Patel","year":"2024","journal-title":"Neuro-Oncology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"e318","DOI":"10.1002\/ctm2.318","article-title":"Identifying circulating glioma cells and their clusters as diagnostic markers by a novel detection platform","volume":"11","author":"Qi","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1093\/neuonc\/noae068","article-title":"Circulating extracellular vesicles as biomarker for diagnosis, prognosis, and monitoring in glioblastoma patients","volume":"26","author":"Ricklefs","year":"2024","journal-title":"Neuro-Oncology"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/neuonc\/noad211","article-title":"Lessons learned from phase 3 trials of immunotherapy for glioblastoma: Time for longitudinal sampling?","volume":"26","author":"Chen","year":"2024","journal-title":"Neuro-Oncology"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"vdab008","DOI":"10.1093\/noajnl\/vdab008","article-title":"Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: To whom do the results of the trials apply?","volume":"3","author":"Skaga","year":"2021","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Alomari, S., Zhang, I., Hernandez, A., Kraft, C.Y., Raj, D., Kedda, J., and Tyler, B. (2021). Drug Repurposing for Glioblastoma and Current Advances in Drug Delivery\u2014A Comprehensive Review of the Literature. Biomolecules, 11.","DOI":"10.3390\/biom11121870"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Ntafoulis, I., Koolen, S.L.W., Leenstra, S., and Lamfers, M.L.M. (2022). Drug Repurposing, a Fast-Track Approach to Develop Effective Treatments for Glioblastoma. Cancers, 14.","DOI":"10.3390\/cancers14153705"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/5\/879\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:46:44Z","timestamp":1760028404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/5\/879"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":179,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["cancers17050879"],"URL":"https:\/\/doi.org\/10.3390\/cancers17050879","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]}}}