Combinatorial approaches to effective therapy in glioblastoma (GBM): Current status and what the future holds

References

• Alexander BM, Cloughesy TF. Adult glioblastoma. J Clin Oncol 2017;35(21):2402–2409. doi:10.1200/JCO.2017.73.0119.
   PubMed Web of Science ®Google Scholar
• Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352(10):987–996. doi:10.1056/NEJMoa043330.
   PubMed Web of Science ®Google Scholar
• Stupp R, Hegi ME, Mason WP, et al. 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. Lancet Oncol 2009;10(5):459–466. doi:10.1016/S1470-2045(09)70025-7.
   PubMed Web of Science ®Google Scholar
• Zhang F, Xu C-L, Liu C-M. Drug delivery strategies to enhance the permeability of the blood–brain barrier for treatment of glioma. Drug Des Devel Ther 2015;9:2089–2100.
   PubMed Web of Science ®Google Scholar
• Huang B, Li X, Li Y, et al. Current immunotherapies for glioblastoma multiforme. Front Immunol 2021;11:3890. doi:10.3389/fimmu.2020.603911.
   Web of Science ®Google Scholar
• Woodworth GF, Dunn GP, Nance EA, et al. Emerging insights into barriers to effective brain tumor therapeutics. Front Oncol 2014;4:126.
   PubMedGoogle Scholar
• Abbott NJ. Blood–brain barrier structure and function and the challenges for CNS drug delivery. J Inherit Metab Dis 2013;36(3):437–449. doi:10.1007/s10545-013-9608-0.
   PubMed Web of Science ®Google Scholar
• Roy L-O, Poirier M-B, Fortin D. Transforming growth factor-beta and its implication in the malignancy of gliomas. Target Oncol 2015;10(1):1–14. doi:10.1007/s11523-014-0308-y.
   PubMed Web of Science ®Google Scholar
• Maas SLN, Abels ER, Van De Haar LL, et al. Glioblastoma hijacks microglial gene expression to support tumor growth. J Neuroinflammation 2020;17(1):1–18. doi:10.1186/s12974-020-01797-2.
   PubMed Web of Science ®Google Scholar
• Abels ER, Maas SLN, Tai E, et al. GlioM&M: web-based tool for studying circulating and infiltrating monocytes and macrophages in glioma. Sci Rep 2020;10(1):1–11. doi:10.1038/s41598-020-66728-w.
   PubMed Web of Science ®Google Scholar
• Andaloussi AE, Han Y, Lesniak MS. Progression of intracranial glioma disrupts thymic homeostasis and induces T-cell apoptosis in vivo. Cancer Immunol Immunother 2008;57(12):1807–1816. doi:10.1007/s00262-008-0508-3.
   PubMed Web of Science ®Google Scholar
• Nduom EK, Wei J, Yaghi NK, et al. PD-L1 expression and prognostic impact in glioblastoma. Neuro Oncol 2016;18(2):195–205. doi:10.1093/neuonc/nov172.
   PubMed Web of Science ®Google Scholar
• Chongsathidkiet P, Jackson C, Koyama S, et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med 2018;24(9):1459–1468. doi:10.1038/s41591-018-0135-2.
   PubMed Web of Science ®Google Scholar
• Zhao J, Chen AX, Gartrell RD, et al. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. Nat Med 2019;25(3):462–469. doi:10.1038/s41591-019-0349-y.
   PubMed Web of Science ®Google Scholar
• Ueda R, Fujita M, Zhu X, et al. Systemic inhibition of transforming growth factor-β in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Clin Cancer Res 2009;15(21):6551–6559. doi:10.1158/1078-0432.CCR-09-1067.
   PubMed Web of Science ®Google Scholar
• Jordan JT, Sun W, Hussain SF, et al. Preferential migration of regulatory T cells mediated by glioma-secreted chemokines can be blocked with chemotherapy. Cancer Immunol Immunother 2008;57(1):123–131. doi:10.1007/s00262-007-0336-x.
   PubMed Web of Science ®Google Scholar
• Singh D, Chan JM, Zoppoli P, et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 2012;337(6099):1231–1235. doi:10.1126/science.1220834.
   PubMed Web of Science ®Google Scholar
• Jackson M, Hassiotou F, Nowak A. Glioblastoma stem-like cells: at the root of tumor recurrence and a therapeutic target. Carcinogenesis 2015;36(2):177–185. doi:10.1093/carcin/bgu243.
   PubMed Web of Science ®Google Scholar
• Yang W, Li Y, Gao R, et al. MHC class I dysfunction of glioma stem cells escapes from CTL-mediated immune response via activation of Wnt/β-catenin signaling pathway. Oncogene 2020;39(5):1098–1111. doi:10.1038/s41388-019-1045-6.
   PubMed Web of Science ®Google Scholar
• Wei J, Barr J, Kong L-Y, et al. Glioblastoma cancer-initiating cells inhibit T-cell proliferation and effector responses by the signal transducers and activators of transcription 3 pathway. Mol Cancer Ther 2010;9(1):67–78. doi:10.1158/1535-7163.MCT-09-0734.
   PubMed Web of Science ®Google Scholar
• Hatterer E, Davoust N, Didier-Bazes M, et al. How to drain without lymphatics? Dendritic cells migrate from the cerebrospinal fluid to the B-cell follicles of cervical lymph nodes. Blood 2006;107(2):806–812. doi:10.1182/blood-2005-01-0154.
   PubMed Web of Science ®Google Scholar
• Goldmann J, Kwidzinski E, Brandt C, et al. T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa. J Leukoc Biol 2006;80(4):797–801. doi:10.1189/jlb.0306176.
   PubMed Web of Science ®Google Scholar
• Belykh E, Shaffer KV, Lin C, et al. Blood-brain barrier, blood-brain tumor barrier, and fluorescence-guided neurosurgical oncology: delivering optical labels to brain tumors. Front Oncol 2020;10:739.
   PubMed Web of Science ®Google Scholar
• Kutuzov N, Flyvbjerg H, Lauritzen M. Contributions of the glycocalyx, endothelium, and extravascular compartment to the blood–brain barrier. Proc Natl Acad Sci USA 2018;115(40):E9429–E9438. doi:10.1073/pnas.1802155115.
   PubMed Web of Science ®Google Scholar
• Haeren RHL, van de Ven SEM, van Zandvoort MAMJ, et al. Assessment and imaging of the cerebrovascular glycocalyx. Curr Neurovasc Res 2016;13(3):249–260.
   PubMed Web of Science ®Google Scholar
• Sweeney MD, Sagare AP, Zlokovic BV. Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 2018;14(3):133–150. doi:10.1038/nrneurol.2017.188.
   PubMed Web of Science ®Google Scholar
• Tietz S, Engelhardt B. Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol 2015;209(4):493–506. doi:10.1083/jcb.201412147.
   PubMed Web of Science ®Google Scholar
• Mathiisen TM, Lehre KP, Danbolt NC, et al. The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 2010;58(9):1094–1103. doi:10.1002/glia.20990.
   PubMed Web of Science ®Google Scholar
• Alvarez JI, Katayama T, Prat A. Glial influence on the blood brain barrier. Glia 2013;61(12):1939–1958. doi:10.1002/glia.22575.
   PubMed Web of Science ®Google Scholar
• Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med 2013;19(12):1584–1596. doi:10.1038/nm.3407.
   PubMed Web of Science ®Google Scholar
• van Tellingen O, Yetkin-Arik B, de Gooijer MC, et al. Overcoming the blood–brain tumor barrier for effective glioblastoma treatment. Drug Resist Updat 2015;19:1–12. doi:10.1016/j.drup.2015.02.002.
   PubMed Web of Science ®Google Scholar
• Boucher Y, Salehi H, Witwer B, et al. Interstitial fluid pressure in intracranial tumours in patients and in rodents. Br J Cancer 1997;75(6):829–836. doi:10.1038/bjc.1997.148.
   PubMed Web of Science ®Google Scholar
• Sarkaria JN, Hu LS, Parney IF, et al. Is the blood–brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro Oncol 2018;20(2):184–191. doi:10.1093/neuonc/nox175.
   PubMed Web of Science ®Google Scholar
• Schlageter KE, Molnar P, Lapin GD, et al. Microvessel organization and structure in experimental brain tumors: microvessel populations with distinctive structural and functional properties. Microvasc Res 1999;58(3):312–328. doi:10.1006/mvre.1999.2188.
   PubMed Web of Science ®Google Scholar
• Groothuis DR. The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. Neuro Oncol 2000;2(1):45–59. doi:10.1215/15228517-2-1-45.
   PubMed Web of Science ®Google Scholar
• Guo H, Kang H, Tong H, et al. Microvascular characteristics of lower-grade diffuse gliomas: investigating vessel size imaging for differentiating grades and subtypes. Eur Radiol 2019;29(4):1893–1902. doi:10.1007/s00330-018-5738-y.
   PubMed Web of Science ®Google Scholar
• Dhermain FG, Hau P, Lanfermann H, et al. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol 2010;9(9):906–920. doi:10.1016/S1474-4422(10)70181-2.
   PubMed Web of Science ®Google Scholar
• Abbott NJ, Rönnbäck L, Hansson E. Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 2006;7(1):41–53. doi:10.1038/nrn1824.
   PubMed Web of Science ®Google Scholar
• Karmur BS, Philteos J, Abbasian A, et al. Blood-brain barrier disruption in neuro-oncology: strategies, failures, and challenges to overcome. Front Oncol 2020;10:563840. doi:10.3389/fonc.2020.563840.
   PubMed Web of Science ®Google Scholar
• Bonavia R, Inda M-d-M, Cavenee WK, Furnari FB. Heterogeneity maintenance in glioblastoma: a social network. Cancer Res 2011;71(12):4055–4060. doi:10.1158/0008-5472.CAN-11-0153.
   PubMed Web of Science ®Google Scholar
• Soeda A, Hara A, Kunisada T, Yoshimura S-i, Iwama T, Park DM. The evidence of glioblastoma heterogeneity. Sci Rep 2015;5(1):1–7. doi:10.1038/srep07979.
   Google Scholar
• Network C. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455(7216):1061.
   PubMed Web of Science ®Google Scholar
• Wang Q, Hu B, Hu X, et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell 2017;32(1):42–56. e6. doi:10.1016/j.ccell.2017.06.003.
   PubMed Web of Science ®Google Scholar
• Verhaak RGW, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17(1):98–110. doi:10.1016/j.ccr.2009.12.020.
   PubMed Web of Science ®Google Scholar
• Fadhlullah SFB, Halim NBA, Yeo JYT, et al. Pathogenic mutations in neurofibromin identifies a leucine-rich domain regulating glioma cell invasiveness. Oncogene 2019;38(27):5367–5380. doi:10.1038/s41388-019-0809-3.
   PubMed Web of Science ®Google Scholar
• Neftel C, Laffy J, Filbin MG, et al. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell 2019;178(4):835–849.e21.
   PubMed Web of Science ®Google Scholar
• Kumar S, Sharife H, Kreisel T, et al. Intra-tumoral metabolic zonation and resultant phenotypic diversification are dictated by blood vessel proximity. Cell Metab 2019;30(1):201–211. e6. doi:10.1016/j.cmet.2019.04.003.
   PubMed Web of Science ®Google Scholar
• Quattrini L, Gelardi ELM, Coviello V, et al. Imidazo [1, 2-a] pyridine derivatives as aldehyde dehydrogenase inhibitors: novel chemotypes to target glioblastoma stem cells. J Med Chem 2020;63(9):4603–4616. doi:10.1021/acs.jmedchem.9b01910.
   PubMed Web of Science ®Google Scholar
• Phan LM, Yeung S-CJ, Lee M-H. Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies. Cancer Biol Med 2014;11(1):1–19. doi:10.7497/j.issn.2095-3941.2014.01.001.
   PubMedGoogle Scholar
• Kalyanaraman B. Teaching the basics of cancer metabolism: developing antitumor strategies by exploiting the differences between normal and cancer cell metabolism. Redox Biol 2017;12:833–842. doi:10.1016/j.redox.2017.04.018.
   PubMed Web of Science ®Google Scholar
• Labak CM, Wang YP, Arora et al. Glucose transport: meeting the metabolic demands of cancer, and applications in glioblastoma treatment. Am J Cancer Res 2016;6(8):1599.
   PubMed Web of Science ®Google Scholar
• Geng F, Cheng X, Wu X, et al. Inhibition of SOAT1 suppresses glioblastoma growth via blocking SREBP-1–mediated lipogenesis. Clin Cancer Res 2016;22(21):5337–5348. doi:10.1158/1078-0432.CCR-15-2973.
   PubMed Web of Science ®Google Scholar
• Obara-Michlewska M, Szeliga M. Targeting glutamine addiction in gliomas. Cancers 2020;12(2):310. doi:10.3390/cancers12020310.
   Web of Science ®Google Scholar
• Mittal D, Sinha D, Barkauskas D, et al. Adenosine 2B receptor expression on cancer cells promotes metastasis. Cancer Res 2016;76(15):4372–4382. doi:10.1158/0008-5472.CAN-16-0544.
   PubMed Web of Science ®Google Scholar
• Ohta A, Gorelik E, Prasad SJ, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci USA 2006;103(35):13132–13137. doi:10.1073/pnas.0605251103.
   PubMed Web of Science ®Google Scholar
• Charles N, Ozawa T, Squatrito M, et al. Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell 2010;6(2):141–152. doi:10.1016/j.stem.2010.01.001.
   PubMed Web of Science ®Google Scholar
• Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004;4(10):762–774. doi:10.1038/nri1457.
   PubMed Web of Science ®Google Scholar
• Wainwright DA, Balyasnikova IV, Chang AL, et al. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clin Cancer Res 2012;18(22):6110–6121. doi:10.1158/1078-0432.CCR-12-2130.
   PubMed Web of Science ®Google Scholar
• Wu A, Wei J, Kong L-Y, et al. Glioma cancer stem cells induce immunosuppressive macrophages/microglia. Neuro Oncol 2010;12(11):1113–1125. doi:10.1093/neuonc/noq082.
   PubMed Web of Science ®Google Scholar
• Charles NA, Holland EC, Gilbertson R, et al. The brain tumor microenvironment. Glia 2011;59(8):1169–1180. doi:10.1002/glia.21136.
   PubMed Web of Science ®Google Scholar
• Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009;462(7274):739–744. doi:10.1038/nature08617.
   PubMed Web of Science ®Google Scholar
• Turcan S, Rohle D, Goenka A, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012;483(7390):479–483. doi:10.1038/nature10866.
   PubMed Web of Science ®Google Scholar
• Calvert AE, Chalastanis A, Wu Y, et al. Cancer-associated IDH1 promotes growth and resistance to targeted therapies in the absence of mutation. Cell Rep 2017;19(9):1858–1873. doi:10.1016/j.celrep.2017.05.014.
   PubMed Web of Science ®Google Scholar
• Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 2011;27:441–464. doi:10.1146/annurev-cellbio-092910-154237.
   PubMed Web of Science ®Google Scholar
• Alzial G, Renoult O, Paris F, et al. Wild-type isocitrate dehydrogenase under the spotlight in glioblastoma. Oncogene 2022;41(5):613–619. doi:10.1038/s41388-021-02056-1.
   PubMed Web of Science ®Google Scholar
• Kaur B, Khwaja FW, Severson EA, et al. Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro Oncol 2005;7(2):134–153. doi:10.1215/S1152851704001115.
   PubMed Web of Science ®Google Scholar
• Monteiro A, Hill R, Pilkington G, et al. The role of hypoxia in glioblastoma invasion. Cells 2017;6(4):45. doi:10.3390/cells6040045.
   PubMed Web of Science ®Google Scholar
• Intlekofer AM, Dematteo RG, Venneti S, et al. Hypoxia induces production of L-2-hydroxyglutarate. Cell Metab 2015;22(2):304–311. doi:10.1016/j.cmet.2015.06.023.
   PubMed Web of Science ®Google Scholar
• Domènech M, Hernández A, Plaja A, et al. Hypoxia: the cornerstone of glioblastoma. IJMS 2021;22(22):12608. doi:10.3390/ijms222212608.
   Google Scholar
• Semenza GL. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol 2002;64(5–6):993–998. doi:10.1016/S0006-2952(02)01168-1.
   PubMed Web of Science ®Google Scholar
• Semenza GL, Jiang BH, Leung SW, et al. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 1996;271(51):32529–32537. doi:10.1074/jbc.271.51.32529.
   PubMed Web of Science ®Google Scholar
• Kelly BD, Hackett SF, Hirota K, et al. Cell type–specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ Res 2003;93(11):1074–1081. doi:10.1161/01.RES.0000102937.50486.1B.
   PubMed Web of Science ®Google Scholar
• Vaupel P, Multhoff G. Revisiting the Warburg effect: historical dogma versus current understanding. J Physiol 2021;599(6):1745–1757. doi:10.1113/JP278810.
   PubMed Web of Science ®Google Scholar
• Lv X, Li J, Zhang C, et al. The role of hypoxia-inducible factors in tumor angiogenesis and cell metabolism. Genes Dis 2017;4(1):19–24. doi:10.1016/j.gendis.2016.11.003.
   PubMed Web of Science ®Google Scholar
• Miska J, Lee-Chang C, Rashidi A, et al. HIF-1α is a metabolic switch between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression of Tregs in glioblastoma. Cell Rep 2019;27(1):226–237. e4. doi:10.1016/j.celrep.2019.03.029.
   PubMed Web of Science ®Google Scholar
• Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 2014;211(5):781–790. doi:10.1084/jem.20131916.
   PubMed Web of Science ®Google Scholar
• Nusblat LM, Carroll MJ, Roth CM. Crosstalk between M2 macrophages and glioma stem cells. Cell Oncol (Dordr) 2017;40(5):471–482. doi:10.1007/s13402-017-0337-5.
   PubMed Web of Science ®Google Scholar
• Coffelt SB, Chen Y-Y, Muthana M, et al. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J Immunol 2011;186(7):4183–4190. doi:10.4049/jimmunol.1002802.
   PubMed Web of Science ®Google Scholar
• Griffioen AW, Damen CA, Martinotti S, et al. Endothelial intercellular adhesion molecule-1 expression is suppressed in human malignancies: the role of angiogenic factors. Cancer Res 1996;56(5):1111–1117.
   PubMed Web of Science ®Google Scholar
• Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res 2009;15(17):5323–5337. doi:10.1158/1078-0432.CCR-09-0737.
   PubMed Web of Science ®Google Scholar
• Yang M, Yuan Y, Zhang H, et al. Prognostic significance of CD147 in patients with glioblastoma. J Neurooncol 2013;115(1):19–26. doi:10.1007/s11060-013-1207-2.
   PubMed Web of Science ®Google Scholar
• Tseng H-c, Xiong W, Badeti S, et al. Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma. Nat Commun 2020;11(1):1–15. doi:10.1038/s41467-020-18444-2.
   PubMed Web of Science ®Google Scholar
• Richman SA, Nunez-Cruz S, Moghimi B, et al. High-affinity GD2-specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model. Cancer Immunol Res 2018;6(1):36–46. doi:10.1158/2326-6066.CIR-17-0211.
   PubMed Web of Science ®Google Scholar
• Morgan RA, Yang JC, Kitano M, et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 2010;18(4):843–851. doi:10.1038/mt.2010.24.
   PubMed Web of Science ®Google Scholar
• Peréz-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 2005;23(22):5235–5246. doi:10.1200/JCO.2005.00.6916.
   PubMed Web of Science ®Google Scholar
• Liu X, Jiang S, Fang C, et al. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res 2015;75(17):3596–3607. doi:10.1158/0008-5472.CAN-15-0159.
   PubMed Web of Science ®Google Scholar
• Smith CC, Beckermann KE, Bortone DS, et al. Endogenous retroviral signatures predict immunotherapy response in clear cell renal cell carcinoma. J Clin Invest 2018;128(11):4804–4820. doi:10.1172/JCI121476.
   PubMed Web of Science ®Google Scholar
• Yu Y-P, Liu P, Nelson J, et al. Identification of recurrent fusion genes across multiple cancer types. Sci Rep 2019;9(1):1–9. doi:10.1038/s41598-019-38550-6.
   PubMedGoogle Scholar
• Hanada K-I, Yewdell JW, Yang JC. Immune recognition of a human renal cancer antigen through post-translational protein splicing. Nature 2004;427(6971):252–256. doi:10.1038/nature02240.
   PubMed Web of Science ®Google Scholar
• Jayasinghe RG, Cao S, Gao Q, et al. Systematic analysis of splice-site-creating mutations in cancer. Cell Rep 2018;23(1):270–281.e3.
   PubMed Web of Science ®Google Scholar
• Dunn GP, Cloughesy TF, Maus MV, et al. Emerging immunotherapies for malignant glioma: from immunogenomics to cell therapy. Neuro Oncol 2020;22(10):1425–1438. doi:10.1093/neuonc/noaa154.
   PubMed Web of Science ®Google Scholar
• Dunn GP, Okada H. Principles of immunology and its nuances in the central nervous system. Neuro Oncol 2015;17(suppl 7):vii3–vii8. doi:10.1093/neuonc/nov175.
   PubMedGoogle Scholar
• Engelhardt B, Vajkoczy P, Weller RO. The movers and shapers in immune privilege of the CNS. Nat Immunol 2017;18(2):123–131. doi:10.1038/ni.3666.
   PubMed Web of Science ®Google Scholar
• Mahlokozera T, Vellimana AK, Li T, et al. Biological and therapeutic implications of multisector sequencing in newly diagnosed glioblastoma. Neuro Oncol 2018;20(4):472–483. doi:10.1093/neuonc/nox232.
   PubMed Web of Science ®Google Scholar
• Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014;344(6190):1396–1401. doi:10.1126/science.1254257.
   PubMed Web of Science ®Google Scholar
• Sottoriva A, Spiteri I, Piccirillo SGM, et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci USA 2013;110(10):4009–4014. doi:10.1073/pnas.1219747110.
   PubMed Web of Science ®Google Scholar
• Hodges TR, Ott M, Xiu J, et al. Mutational burden, immune checkpoint expression, and mismatch repair in glioma: implications for immune checkpoint immunotherapy. Neuro Oncol 2017;19(8):1047–1057. doi:10.1093/neuonc/nox026.
   PubMed Web of Science ®Google Scholar
• Picart T, Berhouma M, Dumot C, et al. Optimization of high-grade glioma resection using 5-ALA fluorescence-guided surgery: a literature review and practical recommendations from the neuro-oncology club of the French society of neurosurgery. Neurochirurgie 2019;65(4):164–177. doi:10.1016/j.neuchi.2019.04.005.
   PubMed Web of Science ®Google Scholar
• Lavrador JP, Baig Mirza A, Ghimire P, et al. A crowdsourced consensus on supratotal resection versus gross total resection for anatomically distinct primary glioblastoma. Neurosurgery 2022;90(3):e71–e71. doi:10.1227/NEU.0000000000001769.
   PubMedGoogle Scholar
• Brown TJ, Brennan MC, Li M, et al. Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol 2016;2(11):1460–1469. doi:10.1001/jamaoncol.2016.1373.
   PubMed Web of Science ®Google Scholar
• Schupper AJ, Roa JA, Hadjipanayis CG. Contemporary intraoperative visualization for GBM with use of exoscope, 5-ALA fluorescence-guided surgery and tractography. Neurosurg Focus 2022;6(1):1–2. doi:10.3171/2021.10.FOCVID21174.
   Google Scholar
• Senft C, Bink A, Franz K, et al. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 2011;12(11):997–1003. doi:10.1016/S1470-2045(11)70196-6.
   PubMed Web of Science ®Google Scholar
• Widhalm G, Olson J, Weller J, et al. The value of visible 5-ALA fluorescence and quantitative protoporphyrin IX analysis for improved surgery of suspected low-grade gliomas. J Neurosurg 2020;133(1):79–88. doi:10.3171/2019.1.JNS182614.
   Web of Science ®Google Scholar
• Moiyadi AV, Shetty PM, Mahajan A, et al. Usefulness of three-dimensional navigable intraoperative ultrasound in resection of brain tumors with a special emphasis on malignant gliomas. Acta Neurochir (Wien) 2013;155(12):2217–2225. doi:10.1007/s00701-013-1881-z.
   PubMed Web of Science ®Google Scholar
• Molinaro AM, Hervey-Jumper S, Morshed RA, et al. Association of maximal extent of resection of contrast-enhanced and non–contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma. JAMA Oncol 2020;6(4):495–503. doi:10.1001/jamaoncol.2019.6143.
   PubMed Web of Science ®Google Scholar
• Redmond KJ, Mehta M. Stereotactic radiosurgery for glioblastoma. Cureus 2015;7(12):e413. doi:10.7759/cureus.413.
   PubMedGoogle Scholar
• Barbarite E, Sick JT, Berchmans E, et al. The role of brachytherapy in the treatment of glioblastoma multiforme. Neurosurg Rev 2017;40(2):195–211. doi:10.1007/s10143-016-0727-6.
   PubMed Web of Science ®Google Scholar
• Kitange GJ, Carlson BL, Schroeder MA, et al. Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts. Neuro Oncol 2009;11(3):281–291. doi:10.1215/15228517-2008-090.
   PubMed Web of Science ®Google Scholar
• Brandes AA, Franceschi E, Tosoni A, et al. Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 2009;115(15):3512–3518. doi:10.1002/cncr.24406.
   PubMed Web of Science ®Google Scholar
• Hegi ME, Diserens A-C, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352(10):997–1003. doi:10.1056/NEJMoa043331.
   PubMed Web of Science ®Google Scholar
• Bhakat KK, Mitra S. CpG methylation-dependent repression of the human O 6-methylguanine-DNA methyltransferase gene linked to chromatin structure alteration. Carcinogenesis 2003;24(8):1337–1345. doi:10.1093/carcin/bgg086.
   PubMed Web of Science ®Google Scholar
• von Bueren AO, Bacolod MD, Hagel C, et al. Mismatch repair deficiency: a temozolomide resistance factor in medulloblastoma cell lines that is uncommon in primary medulloblastoma tumours. Br J Cancer 2012;107(8):1399–1408. doi:10.1038/bjc.2012.403.
   PubMed Web of Science ®Google Scholar
• Weller M, van den Bent M, Tonn JC, et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017;18(6):e315–e329. doi:10.1016/S1470-2045(17)30194-8.
   PubMed Web of Science ®Google Scholar
• Gilbert MR, Dignam J, Won M, et al. RTOG 0825: phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). JCO 2013;31(18_suppl):1–1. doi:10.1200/jco.2013.31.18_suppl.1.
   PubMed Web of Science ®Google Scholar
• Kirson ED, Gurvich Z, Schneiderman R, et al. Disruption of cancer cell replication by alternating electric fields. Cancer Res 2004;64(9):3288–3295. doi:10.1158/0008-5472.can-04-0083.
   PubMed Web of Science ®Google Scholar
• Rominiyi O, Vanderlinden A, Clenton SJ, et al. Tumour treating fields therapy for glioblastoma: current advances and future directions. Br J Cancer 2021;124(4):697–709. doi:10.1038/s41416-020-01136-5.
   PubMed Web of Science ®Google Scholar
• Nardone V, Desideri I, D’Ambrosio L, et al. Nuclear medicine and radiotherapy in the clinical management of glioblastoma patients. Clin Transl Imaging 2022;1–17. doi:10.1007/s40336-022-00495-8. EPUB (ahead of print)
   Web of Science ®Google Scholar
• Wang M, Zhang C, Wang X, et al. Tumor-treating fields (TTFields)-based cocktail therapy: a novel blueprint for glioblastoma treatment. Am J Cancer Res 2021;11(4):1069–1086.
   PubMed Web of Science ®Google Scholar
• Soni VS, Yanagihara TK. Tumor treating fields in the management of Glioblastoma: opportunities for advanced imaging. Cancer Imaging 2019;19(1):1–1.
   Google Scholar
• Aldoghachi AF, Aldoghachi AF, Breyne K, et al. Recent advances in the therapeutic strategies of glioblastoma multiforme. Neuroscience 2022;491:240–270. doi:10.1016/j.neuroscience.2022.03.030.
   PubMed Web of Science ®Google Scholar
• Kodysh J, Rubinsteyn A. OpenVax: an open-source computational pipeline for cancer neoantigen prediction. In: Bioinformatics for cancer immunotherapy. Springer; 2020. pp 147–160.
   Google Scholar
• Jeyapalan SA, Toms SA, Hottinger AF et al. Analysis of the EF-14 phase III trial reveals that tumor treating fields alter progression patterns in glioblastoma. Clin Oncol 2019;37(15_suppl):2055–2055.
   Google Scholar
• Shi W, Kleinberg L, Jeyapalan S et al. Trident phase 3 trial (EF-32): first-line Tumor Treating Fields (TTFields; 200 kHz) concomitant with chemo-radiation, followed by maintenance TTFields/temozolomide in newly diagnosed glioblastoma. Brain Tumor Res Treat 2022;10(Suppl):S153.
   Google Scholar
• Fallah J, Chaudhary RT, Rogers LR et al. Clinical outcomes of the combination of bevacizumab and TTFields in patients with recurrent glioblastoma: results of a phase II clinical trial. Am Soc Clin Oncol 2020;38(15_suppl):2537-2537.
   Google Scholar
• Mason WP, Kesari S, Stupp R et al. Full enrollment results from an extended phase I, multicenter, open label study of marizomib (MRZ) with temozolomide (TMZ) and radiotherapy (RT) in newly diagnosed glioblastoma (GBM). Clin Oncol 2019. 37(15_suppl):2021.
   Google Scholar
• Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 2017;318(23):2306–2316. doi:10.1001/jama.2017.18718.
   PubMed Web of Science ®Google Scholar
• Stupp R, Wong ET, Kanner AA, et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer 2012;48(14):2192–2202. doi:10.1016/j.ejca.2012.04.011.
   PubMed Web of Science ®Google Scholar
• Gil-Gil MJ, Mesia C, Rey M, et al. Bevacizumab for the treatment of glioblastoma. Clin Med Insights Oncol 2013;7:CMO. S8503. doi:10.4137/CMO.S8503.
   Google Scholar
• Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy–temozolomide for newly diagnosed glioblastoma. N Engl J Med 2014;370(8):709–722. doi:10.1056/NEJMoa1308345.
   PubMed Web of Science ®Google Scholar
• Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 2014;370(8):699–708. doi:10.1056/NEJMoa1308573.
   PubMed Web of Science ®Google Scholar
• Ren X, Ai D, Li T, et al. Effectiveness of lomustine combined with bevacizumab in glioblastoma: a meta-analysis. Front Neurol 2021;11:603947. doi:10.3389/fneur.2020.603947.
   PubMed Web of Science ®Google Scholar
• Dwivedi A, Karulkar A, Ghosh S, et al. Robust antitumor activity and low cytokine production by novel humanized anti-CD19 CAR T cells. Mol Cancer Ther 2021;20(5):846–858. doi:10.1158/1535-7163.MCT-20-0476.
   PubMed Web of Science ®Google Scholar
• Brown CE, Badie B, Barish ME, et al. Bioactivity and safety of IL13Rα2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res 2015;21(18):4062–4072. doi:10.1158/1078-0432.CCR-15-0428.
   PubMed Web of Science ®Google Scholar
• O’Rourke DM, Nasrallah MP, Desai A, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med 2017;9(399):eaaa0984. doi:10.1126/scitranslmed.aaa0984.
   PubMed Web of Science ®Google Scholar
• Ahmed N, Brawley V, Hegde M, et al. HER2-specific chimeric antigen receptor–modified virus-specific T cells for progressive glioblastoma: a phase 1 dose-escalation trial. JAMA Oncol 2017;3(8):1094–1101. doi:10.1001/jamaoncol.2017.0184.
   PubMed Web of Science ®Google Scholar
• Majzner RG, Ramakrishna S, Yeom KW, et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature 2022;603(7903):934–910. doi:10.1038/s41586-022-04489-4.
   PubMed Web of Science ®Google Scholar
• Nejo T, Mende A, Okada H. The current state of immunotherapy for primary and secondary brain tumors: similarities and differences. Jpn J Clin Oncol 2020;50(11):1231–1245. doi:10.1093/jjco/hyaa164.
   PubMed Web of Science ®Google Scholar
• Maggs L, Cattaneo G, Dal AE, et al. CAR T cell-based immunotherapy for the treatment of glioblastoma. Front Neurol 2021;15:662064.
   Google Scholar
• Maggs L, Cattaneo G, Dal AE, et al. CAR T cell-based immunotherapy for the treatment of glioblastoma. Front Neurosci 2021;15:535. doi:10.3389/fnins.2021.662064.
   Web of Science ®Google Scholar
• Morgan RA, Johnson LA, Davis JL, et al. Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Hum Gene Ther 2012;23(10):1043–1053. doi:10.1089/hum.2012.041.
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol 2018;15(1):47–62. doi:10.1038/nrclinonc.2017.148.
   PubMed Web of Science ®Google Scholar
• Hegde M, Corder A, Chow KKH, et al. Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma. Mol Ther 2013;21(11):2087–2101. doi:10.1038/mt.2013.185.
   PubMed Web of Science ®Google Scholar
• Hegde M, Mukherjee M, Grada Z, et al. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape. J Clin Invest 2016;126(8):3036–3052. doi:10.1172/JCI83416.
   PubMed Web of Science ®Google Scholar
• Krenciute G, Prinzing BL, Yi Z, et al. Transgenic expression of IL15 improves antiglioma activity of IL13Rα2-CAR T cells but results in antigen loss variants. Cancer Immunol Res 2017;5(7):571–581. doi:10.1158/2326-6066.CIR-16-0376.
   PubMed Web of Science ®Google Scholar
• Shum T, Omer B, Tashiro H, et al. Constitutive signaling from an engineered IL7 receptor promotes durable tumor elimination by tumor-redirected T cells. Cancer Discov 2017;7(11):1238–1247. doi:10.1158/2159-8290.CD-17-0538.
   PubMed Web of Science ®Google Scholar
• Zimmermann K, Kuehle J, Dragon AC, et al. Design and characterization of an “all-in-one” lentiviral vector system combining constitutive anti-GD2 CAR expression and inducible cytokines. Cancers 2020;12(2):375. doi:10.3390/cancers12020375.
   Web of Science ®Google Scholar
• Park S, Pascua E, Lindquist KC, et al. Direct control of CAR T cells through small molecule-regulated antibodies. Nat Commun 2021;12(1):1–10. doi:10.1038/s41467-020-20671-6.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Gao N, Fu Y-L, et al. Generation of regulable EGFRvIII targeted chimeric antigen receptor T cells for adoptive cell therapy of glioblastoma. Biochem Biophys Res Commun 2018;507(1–4):59–66. doi:10.1016/j.bbrc.2018.10.151.
   PubMed Web of Science ®Google Scholar
• Labanieh L, Majzner RG, Klysz D, et al. Enhanced safety and efficacy of protease-regulated CAR-T cell receptors. Cell 2022;185(10):1745–1763.e22. doi:10.1016/j.cell.2022.03.041.
   PubMed Web of Science ®Google Scholar
• Clackson T, Yang W, Rozamus LW, et al. Redesigning an FKBP–ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci USA 1998;95(18):10437–10442. doi:10.1073/pnas.95.18.10437.
   PubMed Web of Science ®Google Scholar
• Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a “safety switch” to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol 2014;5:235.
   Google Scholar
• Pulè MA, Straathof KC, Dotti G, et al. A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther 2005;12(5):933–941. doi:10.1016/j.ymthe.2005.04.016.
   PubMed Web of Science ®Google Scholar
• Pule MA, Savoldo B, Myers GD, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med 2008;14(11):1264–1270. doi:10.1038/nm.1882.
   PubMed Web of Science ®Google Scholar
• Louis CU, Savoldo B, Dotti G, et al. Antitumor activity and long-term fate of chimeric antigen receptor–positive T cells in patients with neuroblastoma. Blood 2011;118(23):6050–6056. doi:10.1182/blood-2011-05-354449.
   PubMed Web of Science ®Google Scholar
• Gargett T, Fraser CK, Dotti G, et al. BRAF and MEK inhibition variably affect GD2-specific chimeric antigen receptor (CAR) T-cell function in vitro. J Immunother 2015;38(1):12–23. doi:10.1097/CJI.0000000000000061.
   PubMed Web of Science ®Google Scholar
• Zajc CU, Dobersberger M, Schaffner I, et al. A conformation-specific ON-switch for controlling CAR T cells with an orally available drug. Proc Natl Acad Sci USA 2020;117(26):14926–14935. doi:10.1073/pnas.1911154117.
   PubMed Web of Science ®Google Scholar
• Leung W-H, Gay J, Martin U, et al. Sensitive and adaptable pharmacological control of CAR T cells through extracellular receptor dimerization. JCI Insight 2019;4(11):e124430. doi:10.1172/jci.insight.124430.
   Web of Science ®Google Scholar
• Wu C-Y, Roybal KT, Puchner EM, et al. Remote control of therapeutic T cells through a small molecule–gated chimeric receptor. Science 2015;350(6258):aab4077.
   PubMed Web of Science ®Google Scholar
• Rousso-Noori L, Mastandrea I, Talmor S, et al. P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas. Nat Commun 2021;12(1):1–13. doi:10.1038/s41467-021-23817-2.
   PubMed Web of Science ®Google Scholar
• de Billy E, Pellegrino M, Orlando D, et al. Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant. Neuro-oncology 2022;24(7):1150–1163. doi:10.1093/neuonc/noab300.
   PubMed Web of Science ®Google Scholar
• Land CA, Musich PR, Haydar D, et al. Chimeric antigen receptor T-cell therapy in glioblastoma: charging the T cells to fight. J Transl Med 2020;18(1):1–13. doi:10.1186/s12967-020-02598-0.
   PubMed Web of Science ®Google Scholar
• Wang D, Starr R, Chang W-C, et al. Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma. Sci Transl Med 2020;12(533):eaaw2672. doi:10.1126/scitranslmed.aaw2672.
   PubMed Web of Science ®Google Scholar
• Liau LM, et al. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med 2018;16(1):1–9.
   PubMedGoogle Scholar
• Wen PY, Reardon DA, Armstrong TS, et al. A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma. Clin Cancer Res 2019;25(19):5799–5807. doi:10.1158/1078-0432.CCR-19-0261.
   PubMed Web of Science ®Google Scholar
• Van Gool SW, Makalowski J, Fiore S, et al. Randomized controlled immunotherapy clinical trials for GBM challenged. Cancers 2020;13(1):32. doi:10.3390/cancers13010032.
   Web of Science ®Google Scholar
• Yu J, Sun H, Cao W, et al. Research progress on dendritic cell vaccines in cancer immunotherapy. Exp Hematol Oncol 2022;11(1):1–22. doi:10.1186/s40164-022-00257-2.
   PubMed Web of Science ®Google Scholar
• Ghorbaninezhad F, Asadzadeh Z, Masoumi J, et al. Dendritic cell-based cancer immunotherapy in the era of immune checkpoint inhibitors: from bench to bedside. Life Sci 2022;297:120466. doi:10.1016/j.lfs.2022.120466.
   PubMed Web of Science ®Google Scholar
• Hu JL, Omofoye OA, Rudnick JD, et al. A phase I study of autologous dendritic cell vaccine pulsed with allogeneic stem-like cell line lysate in patients with newly diagnosed or recurrent glioblastoma. Clin Cancer Res 2022;28(4):689–696. doi:10.1158/1078-0432.CCR-21-2867.
   PubMed Web of Science ®Google Scholar
• Bryukhovetskiy I. Cell‑based immunotherapy of glioblastoma multiforme. Oncol Lett 2022;23(4):1–14. doi:10.3892/ol.2022.13253.
   PubMed Web of Science ®Google Scholar
• Vik-Mo EO, Nyakas M, Mikkelsen BV, et al. Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol Immunother 2013;62(9):1499–1509. doi:10.1007/s00262-013-1453-3.
   PubMed Web of Science ®Google Scholar
• Markov O, Oshchepkova A, Mironova N. Immunotherapy based on dendritic cell-targeted/-derived extracellular vesicles—a novel strategy for enhancement of the anti-tumor immune response. Front Pharmacol 2019;10:1152. doi:10.3389/fphar.2019.01152.
   PubMed Web of Science ®Google Scholar
• Rapp M, Grauer OM, Kamp M, et al. A randomized controlled phase II trial of vaccination with lysate-loaded, mature dendritic cells integrated into standard radiochemotherapy of newly diagnosed glioblastoma (GlioVax): study protocol for a randomized controlled trial. Trials 2018;19(1):1–14. doi:10.1186/s13063-018-2659-7.
   PubMedGoogle Scholar
• Bota DA, Piccioni DE, Duma CM, et al. CTIM-33. Phase II trial of vaccine immunotherapy in primary glioblastoma: adjunctive autologous dendritic cells pulsed with lysate from irradiated self-renewing autologous tumor cells (AV-GBM-1). Neuro-Oncology 2021;23(Supplement_6):vi58–vi58. doi:10.1093/neuonc/noab196.225.
   Google Scholar
• Kelly WJ, Giles AJ, Gilbert M. T lymphocyte-targeted immune checkpoint modulation in glioma. J Immunother Cancer 2020;8(1):e000379. doi:10.1136/jitc-2019-000379.
   PubMed Web of Science ®Google Scholar
• Inoges S, Tejada S, de Cerio A, et al. A phase II trial of autologous dendritic cell vaccination and radiochemotherapy following fluorescence-guided surgery in newly diagnosed glioblastoma patients. J Transl Med 2017;15(1):104.
   PubMed Web of Science ®Google Scholar
• Cozzi S, Najafi M, Gomar M, et al. Delayed effect of dendritic cells vaccination on survival in glioblastoma: a systematic review and meta-analysis. Curr Oncol 2022;29(2):881–891. doi:10.3390/curroncol29020075.
   PubMed Web of Science ®Google Scholar
• Yan Y, Zeng S, Gong Z, et al. Clinical implication of cellular vaccine in glioma: current advances and future prospects. J Exp Clin Cancer Res 2020;39(1):1–18. doi:10.1186/s13046-020-01778-6.
   PubMed Web of Science ®Google Scholar
• Woroniecka K, Fecci PE. Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma. Neuro Oncol 2020;22(9):1233–1234. doi:10.1093/neuonc/noaa170.
   PubMed Web of Science ®Google Scholar
• Preddy I, et al. Checkpoint: inspecting the barriers in glioblastoma immunotherapies. In: Seminars in cancer biology. Elsevier; 2022. doi:10.1016/j.semcancer.2022.02.012.
   Google Scholar
• Armstrong TS, Wen P, Reardon DA et al. Comparative impact of treatment on clinical benefit in patients with glioblastoma (GBM) enrolled in the phase II trial of ICT-107. Clin Oncol 2015;33(15_suppl):2036–2036.
   Google Scholar
• Van Woensel M, Mathivet T, Wauthoz N, et al. Sensitization of glioblastoma tumor micro-environment to chemo-and immunotherapy by Galectin-1 intranasal knock-down strategy. Sci Rep 2017;7(1):1–14. doi:10.1038/s41598-017-01279-1.
   PubMedGoogle Scholar
• Ojima T, Iwahashi M, Nakamura M, et al. The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendritic cells expressing tumor-associated antigen. Int J Oncol 2006;28(4):947–953.
   Google Scholar
• Chen X, He J, Chang L-J. Alteration of T cell immunity by lentiviral transduction of human monocyte-derived dendritic cells. Retrovirology 2004;1(1):37–12. doi:10.1186/1742-4690-1-37.
   PubMedGoogle Scholar
• Mitchell DA, Batich KA, Gunn MD, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature 2015;519(7543):366–369. doi:10.1038/nature14320.
   PubMed Web of Science ®Google Scholar
• Rahman M, Ghiaseddin A, Yegorov O, et al. ATIM-15. Sustained complete radiographic response and prolonged systemic immune activation in a patient with MGMT unmethylated midline glioblastoma receiving CMV pp65-LAMP RNA-pulsed dendritic cell vaccines. Neuro-oncology 2019;21(Supplement_6):vi4–vi4. doi:10.1093/neuonc/noz175.015.
   Google Scholar
• Parkhurst MR, DePan C, Riley JP, et al. Hybrids of dendritic cells and tumor cells generated by electrofusion simultaneously present immunodominant epitopes from multiple human tumor-associated antigens in the context of MHC class I and class II molecules. J Immunol 2003;170(10):5317–5325. doi:10.4049/jimmunol.170.10.5317.
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Hodi FS, Weber JS, et al. Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma. Ann N Y Acad Sci 2013;1291(1):1–3.
   Google Scholar
• Nayak L, Molinaro AM, Peters K, et al. Randomized phase II and biomarker study of pembrolizumab plus bevacizumab versus pembrolizumab alone for patients with recurrent glioblastoma. Clin Cancer Res 2021;27(4):1048–1057. doi:10.1158/1078-0432.CCR-20-2500.
   PubMed Web of Science ®Google Scholar
• Liu F, Huang J, Liu X, et al. CTLA-4 correlates with immune and clinical characteristics of glioma. Cancer Cell Int 2020;20(1):1–10. doi:10.1186/s12935-019-1085-6.
   PubMed Web of Science ®Google Scholar
• Goswami S, Walle T, Cornish AE, et al. Immune profiling of human tumors identifies CD73 as a combinatorial target in glioblastoma. Nat Med 2020;26(1):39–46. doi:10.1038/s41591-019-0694-x.
   PubMed Web of Science ®Google Scholar
• Iorgulescu JB, Reardon DA, Chiocca EA, et al. Immunotherapy for glioblastoma: going viral. Nature Medicine 2018;24(8):1094–1096.
   Google Scholar
• Ayush P, Ravi M, Lim M. Alternative checkpoints as targets for immunotherapy. Curr Oncol Rep 2020;22(12):126–136. doi:10.1007/s11912-020-00983-y.
   Web of Science ®Google Scholar
• Brown M, McKay Z, Yang Y, et al. 739 Intratumor childhood vaccine-specific CD4+ T cell recall helps antitumor CD8 T cells. J Immunother Cancer 2021;9(Suppl 2):A770–A770. doi:10.1136/jitc-2021-SITC2021.739.
   Google Scholar
• Platten M, Friedrich M, Wainwright DA, et al. Tryptophan metabolism in brain tumors—IDO and beyond. Curr Opin Immunol 2021;70:57–66. doi:10.1016/j.coi.2021.03.005.
   PubMed Web of Science ®Google Scholar
• Cacciotti C, Choi J, Alexandrescu S, et al. Immune checkpoint inhibition for pediatric patients with recurrent/refractory CNS tumors: a single institution experience. J Neurooncol 2020;149(1):113–122. doi:10.1007/s11060-020-03578-6.
   PubMed Web of Science ®Google Scholar
• De La Fuente MI, Coleman H, Rosenthal Met et al. A phase Ib/II study of olutasidenib in patients with relapsed/refractory IDH1 mutant gliomas: safety and efficacy as single agent and in combination with azacitidine. Clin Oncol 2020;38(15_suppl):25805–2505.
   Web of Science ®Google Scholar
• Theruvath J, Menard M, Smith BAH et al. Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nat Med 2022;28(2):333–344. doi:10.1038/s41591-021-01625-x.
   Web of Science ®Google Scholar
• Lequeux A, Noman MZ, Xiao M, et al. Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints. Cancer Lett 2019;458:13–20. doi:10.1016/j.canlet.2019.05.021.
   PubMed Web of Science ®Google Scholar
• Yang F, He Z, Duan H, et al. Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40. Nat Commun 2021;12(1):1–15. doi:10.1038/s41467-021-23832-3.
   PubMed Web of Science ®Google Scholar
• Macedo N, Miller DM, Haq R, et al. Clinical landscape of oncolytic virus research in 2020. J Immunother Cancer 2020;8(2):e001486. doi:10.1136/jitc-2020-001486.
   PubMed Web of Science ®Google Scholar
• Lang FF, Conrad C, Gomez-Manzano C, et al. Phase I study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: replication and immunotherapeutic effects in recurrent malignant glioma. J Clin Oncol 2018;36(14):1419–1427. doi:10.1200/JCO.2017.75.8219.
   PubMed Web of Science ®Google Scholar
• Friedman GK, Johnston JM, Bag AK, et al. Oncolytic HSV-1 G207 immunovirotherapy for pediatric high-grade gliomas. N Engl J Med 2021;384(17):1613–1622. doi:10.1056/NEJMoa2024947.
   PubMed Web of Science ®Google Scholar
• Chiocca EA, Lukas RV, Chen CC, et al. Controlled IL-12 in combination with a PD-1 inhibitor subjects with recurrent glioblastoma. JCO 2020;38(15_suppl):2510–2510. doi:10.1200/JCO.2019.37.15_suppl.2020.
   PubMed Web of Science ®Google Scholar
• Desbaillets N, Hottinger AF. Immunotherapy in Glioblastoma: A Clinical Perspective. Cancers 2021;13(15):3721.
   Google Scholar
• Loya J, Zhang C, Cox E, et al. Biological intratumoral therapy for the high-grade glioma part II: vector-and cell-based therapies and radioimmunotherapy. CNS Oncol 2019;8(3):CNS40. doi:10.2217/cns-2019-0002.
   PubMedGoogle Scholar
• Suryawanshi YR, Schulze AJ. Oncolytic viruses for malignant glioma: on the verge of success? Viruses 2021;13(7):1294. doi:10.3390/v13071294.
   PubMed Web of Science ®Google Scholar
• Ene CI, Fueyo J, Lang FF. Delta-24 adenoviral therapy for glioblastoma: evolution from the bench to bedside and future considerations. Neurosurg Focus 2021;50(2):E6. doi:10.3171/2020.11.FOCUS20853.
   PubMed Web of Science ®Google Scholar
• Maxwell R, Jackson CM, Lim M. Clinical trials investigating immune checkpoint blockade in glioblastoma. Curr Treat Options Oncol 2017;18(8):1–22. doi:10.1007/s11864-017-0492-y.
   PubMed Web of Science ®Google Scholar
• Gromeier M, Lachmann S, Rosenfeld MR, et al. Intergeneric poliovirus recombinants for the treatment of malignant glioma. Proc Natl Acad Sci USA 2000;97(12):6803–6808. doi:10.1073/pnas.97.12.6803.
   PubMed Web of Science ®Google Scholar
• Desjardins A, Gromeier M, Herndon JE, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med 2018;379(2):150–161. doi:10.1056/NEJMoa1716435.
   PubMed Web of Science ®Google Scholar
• Grosser R, Cherkassky L, Chintala N, et al. Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors. Cancer Cell 2019;36(5):471–482. doi:10.1016/j.ccell.2019.09.006.
   PubMed Web of Science ®Google Scholar
• Ma X, Shou P, Smith C, et al. Interleukin-23 engineering improves CAR T cell function in solid tumors. Nat Biotechnol 2020;38(4):448–459. doi:10.1038/s41587-019-0398-2.
   PubMed Web of Science ®Google Scholar
• Huang J, Zheng M, Zhang Z, et al. Interleukin-7-loaded oncolytic adenovirus improves CAR-T cell therapy for glioblastoma. Cancer Immunol Immunother 2021;70(9):2453–2465. doi:10.1007/s00262-021-02856-0.
   PubMed Web of Science ®Google Scholar
• Adams LK, Lyon DY, Alvarez PJ. Comparative eco-toxicity of nanoscale TiO2, SiO2, and ZnO water suspensions. Water Res 2006;40(19):3527–3532. doi:10.1016/j.watres.2006.08.004.
   PubMed Web of Science ®Google Scholar
• Davis A, Morris KV, Shevchenko G. Hypoxia-directed tumor targeting of CRISPR-Cas9 and HSV-TK suicide gene therapy using lipid nanoparticles. Mol Ther Methods Clin Dev 2022;25:158–169. doi:10.1016/j.omtm.2022.03.008.
   PubMed Web of Science ®Google Scholar
• Yu D, Khan OF, Suvà ML, et al. Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression. Proc Natl Acad Sci USA 2017;114(30):E6147–E6156. doi:10.1073/pnas.1701911114.
   PubMed Web of Science ®Google Scholar
• Yang Q, Zhou Y, Chen J, et al. Gene therapy for drug-resistant glioblastoma via lipid-polymer hybrid nanoparticles combined with focused ultrasound. Int J Nanomedicine 2021;16:185–199.
   PubMed Web of Science ®Google Scholar
• Chen J, Dai Q, Yang Q, et al. Therapeutic nucleus-access BNCT drug combined CD47-targeting gene editing in glioblastoma. J Nanobiotechnol 2022;20(1):1–18. doi:10.1186/s12951-022-01304-0.
   PubMed Web of Science ®Google Scholar
• Costa PM, Cardoso AL, Mendonça LS, et al. Tumor-targeted chlorotoxin-coupled nanoparticles for nucleic acid delivery to glioblastoma cells: a promising system for glioblastoma treatment. Mol Ther Nucleic Acids 2013;2:e100. doi:10.1038/mtna.2013.30.
   PubMedGoogle Scholar
• Costa PM, Cardoso AL, Custódia C, et al. MiRNA-21 silencing mediated by tumor-targeted nanoparticles combined with sunitinib: a new multimodal gene therapy approach for glioblastoma. J Control Release 2015;207:31–39. doi:10.1016/j.jconrel.2015.04.002.
   PubMed Web of Science ®Google Scholar
• de Lima LS, Mortari MR. Therapeutic nanoparticles in the brain: a review of types, physicochemical properties and challenges. Int J Pharm 2022;612:121367. doi:10.1016/j.ijpharm.2021.121367.
   PubMedGoogle Scholar
• Kumthekar P, C ko CH, Paunesku T, et al. A first-in-human phase 0 clinical study of RNA interference-based spherical nucleic acids in patients with recurrent glioblastoma. Sci Transl Med 2021;13(584):eabb3945. doi:10.1126/scitranslmed.abb3945.
   Google Scholar
• Mathen P, Rowe L, Mackey M, et al. Radiosensitizers in the temozolomide era for newly diagnosed glioblastoma. Neurooncol Pract 2020;7(3):268–276. doi:10.1093/nop/npz057.
   PubMed Web of Science ®Google Scholar