Single vs. combination immunotherapeutic strategies for glioma

References

• Network TCGAR. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. New England J Med. 2015;372(26):2481–2498.
   PubMed Web of Science ®Google Scholar
• Ostrom QT, Bauchet L, Davis FG, et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro Oncol. 2014;16(7):896–913.
   PubMed Web of Science ®Google Scholar
• Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England J Med. 2005;352(10):987–996.
   PubMed Web of Science ®Google Scholar
• Lowenstein PR, Kroeger K, Castro MG. Immunology of neurological gene therapy: how T cells modulate viral vector-mediated therapeutic transgene expression through immunological synapses. Neurotherapeutics: J Am Soc Exp Neurotherapeutics. 2007;4(4):715–724.
   PubMed Web of Science ®Google Scholar
• Barcia C, Jimenez-Dalmaroni M, Kroeger KM, et al. One-year expression from high-capacity adenoviral vectors in the brains of animals with pre-existing anti-adenoviral immunity: clinical implications. Mol Ther. 2007;15(12):2154–2163.
   PubMed Web of Science ®Google Scholar
• Barcia C, Thomas CE, Curtin JF, et al. In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain. J Exp Med. 2006;203(9):2095–2107.
   PubMed Web of Science ®Google Scholar
• Lowenstein PR, Castro MG. Recent advances in the pharmacology of neurological gene therapy. Curr Opin Pharmacol. 2004;4(1):91–97.
   PubMed Web of Science ®Google Scholar
• Galea I, Bernardes-Silva M, Forse PA, et al. An antigen-specific pathway for CD8 T cells across the blood-brain barrier. J Exp Med. 2007;204(9):2023–2030.
   PubMed Web of Science ®Google Scholar
• Klein RS, Garber C, Howard N. Infectious immunity in the central nervous system and brain function. Nat Immunol. 2017;18(2):132–141.
   PubMed Web of Science ®Google Scholar
• Savarin C, Bergmann Cornelia C, Hinton David R, et al. MMP-independent role of TIMP-1 at the blood brain barrier during viral encephalomyelitis. ASN Neuro. 2013;5(5):e00127.
   Web of Science ®Google Scholar
• Davies DC. Blood–brain barrier breakdown in septic encephalopathy and brain tumours. J Anat. 2002;200(6):639–646.
   PubMed Web of Science ®Google Scholar
• D’Agostino PM, Gottfried-Blackmore A, Anandasabapathy N, et al. Brain dendritic cells: biology and pathology. Acta Neuropathol. 2012;124(5):599–614.
   PubMed Web of Science ®Google Scholar
• Louveau A, Harris TH, Kipnis J. Revisiting the mechanisms of CNS immune privilege. Trends Immunol. 2015;36(10):569–577.
   PubMed Web of Science ®Google Scholar
• Perng P, Lim M. Immunosuppressive mechanisms of malignant gliomas: parallels at non-CNS sites. Front Oncol. 2015;5:153.
   PubMed Web of Science ®Google Scholar
• Nduom EK, Weller M, Heimberger AB. Immunosuppressive mechanisms in glioblastoma. Neuro Oncol. 2015;17(suppl7):vii9–vii14.
   PubMed Web of Science ®Google Scholar
• Appin CL, Brat DJ. Biomarker-driven diagnosis of diffuse gliomas. Mol Aspects Med. 2015;45:87–96.
   PubMed Web of Science ®Google Scholar
• Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–820.
   PubMed Web of Science ®Google Scholar
• Lai AA. Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin. J Clin Oncol. 2011;29(34):4482–4490.
   PubMed Web of Science ®Google Scholar
• Paugh B. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol. 2010;28(18):3061–3068.
   PubMed Web of Science ®Google Scholar
• Sturm D, Bender S, Jones DTW, et al. Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat Rev Cancer. 2014;14(2):92–107.
   PubMed Web of Science ®Google Scholar
• Fontebasso AM, Liu X-Y, Sturm D, et al. Chromatin remodeling defects in pediatric and young adult glioblastoma: a tale of a variant histone 3 tail. Brain Pathol. 2013;23(2):210–216.
   PubMed Web of Science ®Google Scholar
• Siegal T. Clinical relevance of prognostic and predictive molecular markers in gliomas. In: Schramm J, ed. Advances and technical standards in neurosurgery: volume 43. Cham: Springer International Publishing; 2016. p. 91–108.
   Google Scholar
• Koschmann CC. ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma. Sci Transl Med. 2016;8(328):328ra28–28ra28.
   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.
   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 U S A. 2013;110(10):4009–4014.
   PubMed Web of Science ®Google Scholar
• Pellegatta S, Cuppini L, Finocchiaro G. Brain cancer immunoediting: novel examples provided by immunotherapy of malignant gliomas. Expert Rev Anticancer Ther. 2011;11:1759–1774.
   PubMed Web of Science ®Google Scholar
• Sampson JH, Heimberger AB, Archer GE, et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010;28(31):4722–4729.
   PubMed Web of Science ®Google Scholar
• Ohm JE, Carbone DP. VEGF as a mediator of tumor-associated immunodeficiency. Immunol Res. 2001;23(2):263–272.
   PubMed Web of Science ®Google Scholar
• Qiu B, Zhang D, Wang C, et al. IL-10 and TGF-β2 are overexpressed in tumor spheres cultured from human gliomas. Mol Biol Rep. 2011;38(5):3585–3591.
   PubMed Web of Science ®Google Scholar
• Wainwright DADA. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clinical Cancer Research. 2012;18(22):6110–6121.
   PubMed Web of Science ®Google Scholar
• Fecci PE. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res (Chicago, Ill). 2006;66(6):3294–3302.
   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.
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–174.
   PubMed Web of Science ®Google Scholar
• Mirghorbani MM. Myeloid-derived suppressor cells in glioma. Expert Rev Neurother. 2013;13(12):1395–1406.
   PubMed Web of Science ®Google Scholar
• Didenko VV, Ngo HN, Minchew C, et al. Apoptosis of T lymphocytes invading glioblastomas multiforme: a possible tumor defense mechanism. J Neurosurg. 2002;96(3):580–584.
   PubMed Web of Science ®Google Scholar
• Wintterle S, Schreiner B, Mitsdoerffer M, et al. Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer ResMech Immune Para. 2003;63(21):7462–7467.
   Google Scholar
• Brunet J-F, Denizot F, Luciani M-F, et al. A new member of the immunoglobulin superfamily–CTLA-4. Nature. 1987;328(6127):267–270.
   PubMed Web of Science ®Google Scholar
• Takahashi T, Tagami T, Yamazaki S, et al. Immunologic self-tolerance maintained by CD25+ CD4+ regulatory T cells constitutively expressing cytotoxic T lymphocyte–associated antigen 4. J Exp Med. 2000;192(2):303.
   PubMed Web of Science ®Google Scholar
• Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 2002;3(7):611–618.
   PubMed Web of Science ®Google Scholar
• Schwartz RHR. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell (Cambridge). 1992;71(7):1065–1068.
   PubMed Web of Science ®Google Scholar
• Linsley PSP. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity (Cambridge, Mass). 1994;1(9):793–801.
   Google Scholar
• Calinescu AA, Kamran N, Baker G, et al. Overview of current immunotherapeutic strategies for glioma. Immunotherapy. 2015;7(10):1073–1104.
   PubMed Web of Science ®Google Scholar
• Reardon DA, Freeman G, Wu C, et al. Immunotherapy advances for glioblastoma. Neuro Oncol. 2014;16(11):1441–1458.
   PubMed Web of Science ®Google Scholar
• Binder DC. Immunotherapy for cancer in the central nervous system: current and future directions. Oncoimmunology. 2016;5(2):e1082027.
   PubMed Web of Science ®Google Scholar
• Mitchell DA, Fecci PE, Sampson JH. Immunotherapy of malignant brain tumors. Immunol Rev. 2008;222(1):70–100.
   PubMed Web of Science ®Google Scholar
• Kamran N, Calinescu A, Candolfi M, et al. Recent advances and future of immunotherapy for glioblastoma. Expert Opin Biol Ther. 2016;16(10):1245–1264.
   PubMed Web of Science ®Google Scholar
• Hatanpaa KJ, Burma S, Zhao D, et al. Epidermal growth factor receptor in glioma: signal transduction, neuropathology, imaging, and radioresistance. Neoplasia (New York, NY). 2010;12(9):675–684.
   PubMed Web of Science ®Google Scholar
• Schuster J, Lai RK, Recht LD, et al. A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study. Neuro Oncol. 2015;17(6):854–861.
   PubMed Web of Science ®Google Scholar
• CelldexTherapeutics. Data safety and monitoring board recommends Celldex’s phase 3 study of RINTEGA® (rindopepimut) in newly diagnosed glioblastoma be discontinued as it is unlikely to meet primary overall survival endpoint in patients with minimal residual disease. Press Release. 2016. Available from: http://ir.celldex.com/releasedetail.cfm?ReleaseID=959021
   Google Scholar
• Mineharu Y, Castro MG, Lowenstein PR, et al. Dendritic cell-based immunotherapy for glioma: multiple regimens and implications in clinical trials. Neurol Med Chir (Tokyo). 2013;53(11):741–754.
   PubMed Web of Science ®Google Scholar
• Prins RM, Soto H, Konkankit V, et al. Gene expression profile correlates with T cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res. 2011;17(6):1603–1615.
   PubMed Web of Science ®Google Scholar
• Okada H, Kalinski P, Ueda R, et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol: Official J Am Soc Clin Oncol. 2011;29(3):330–336.
   PubMed Web of Science ®Google Scholar
• Phuphanich S, Wheeler CJ, Rudnick JD, et al. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother: CII. 2013;62(1):125–135.
   PubMed Web of Science ®Google Scholar
• Hdeib A, Sloan AE. Dendritic cell immunotherapy for solid tumors: evaluation of the DCVax(R) platform in the treatment of glioblastoma multiforme. CNS Oncol. 2015;4(2):63–69.
   PubMedGoogle Scholar
• Wainwright D. Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors. Clin Cancer Res. 2014;20(20):5290–5301.
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. New England J Med. 2013;369(2):122–133.
   PubMed Web of Science ®Google Scholar
• Agarwalla P, Barnard Z, Fecci P, et al. Sequential immunotherapy by vaccination with GM-CSF expressing glioma cells and CTLA-4 blockade effectively treats established murine intracranial tumors. J Immuno Ther (Hagerstown, Md: 1997). 2012;35(5):385–389.
   PubMed Web of Science ®Google Scholar
• Duraiswamy JJ. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res (Chicago, Ill). 2013;73(12):3591–3603.
   PubMed Web of Science ®Google Scholar
• Williams ELEL. Immunomodulatory monoclonal antibodies combined with peptide vaccination provide potent immunotherapy in an aggressive murine neuroblastoma model. Clin Cancer Res. 2013;19(13):3545–3555.
   PubMed Web of Science ®Google Scholar
• Weber JSJS. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol. 2013;31(34):4311–4318.
   PubMed Web of Science ®Google Scholar
• Maus MV. Designing CAR T cells for glioblastoma. Oncoimmunology. 2015;4(12):e1048956.
   PubMed Web of Science ®Google Scholar
• Sengupta S, Mao G, Gokaslan ZS, et al. Chimeric antigen receptors for treatment of glioblastoma: a practical review of challenges and ways to overcome them. Cancer Gene Ther. 2016;00:1–9.
   Google Scholar
• Kakarla S, Gottschalk S. CAR T cells for solid tumors: armed and ready to go? Cancer J (Sudbury, Mass). 2014;20(2):151–155.
   PubMed Web of Science ®Google Scholar
• Cherkassky L, Morello A, Villena-Vargas J, et al. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest. 2016;126(8):3130–3144.
   PubMed Web of Science ®Google Scholar
• Kosaka A, Ohkuri T, Okada H. Combination of an agonistic anti-CD40 monoclonal antibody and the COX-2 inhibitor celecoxib induces anti-glioma effects by promotion of type-1 immunity in myeloid cells and T-cells. Cancer Immuno Immunother. 2014;63(8):847–857.
   PubMed Web of Science ®Google Scholar
• Moertel CL, Xia J, LaRue R, et al. CD200 in CNS tumor-induced immunosuppression: the role for CD200 pathway blockade in targeted immunotherapy. J Immunother Cancer. 2014;2(1):46.
   PubMedGoogle Scholar
• Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012;12(4):269–281.
   PubMed Web of Science ®Google Scholar
• Madany M, Thomas TM, Edwards L, et al. Immunobiology and immunotherapeutic targeting of glioma stem cells. Adv Exp Med Biol. 2015;853:139–166.
   PubMed Web of Science ®Google Scholar
• Lin R, Sampson JH, Li Q-J, et al. miR-23a blockade enhances adoptive T cell transfer therapy by preserving immune-competence in the tumor microenvironment. Oncoimmunology. 2015;4(3):e990803.
   PubMed Web of Science ®Google Scholar
• Lin R, Chen L, Chen G, et al. Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression. J Clin Investig. 2014;124:5352–5367.
   PubMed Web of Science ®Google Scholar
• Curtin JF, Liu N, Candolfi M, et al. HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med. 2009;6(1):e10.
   PubMed Web of Science ®Google Scholar
• Candolfi M, Kroeger KM, Muhammad AK, et al. Gene therapy for brain cancer: combination therapies provide enhanced efficacy and safety. Curr Gene Ther. 2009;9(5):409–421.
   PubMed Web of Science ®Google Scholar
• Okada H, Giezeman-Smits KM, Tahara H, et al. Effective cytokine gene therapy against an intracranial glioma using a retrovirally transduced IL-4 plus HSVtk tumor vaccine. Gene Ther. 1999;6(2):219–226.
   PubMed Web of Science ®Google Scholar
• Okada H, Lieberman FS, Walter KA, et al. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas. J Transl Med. 2007;5:67.
   PubMed Web of Science ®Google Scholar
• Patel DM, Foreman PM, Nabors LB, et al. Design of a phase I clinical trial to evaluate M032, a genetically engineered HSV-1 expressing IL-12, in patients with recurrent/progressive glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma. Hum Gene Ther Clin Dev. 2016;27(2):69–78.
   PubMed Web of Science ®Google Scholar
• Mineharu Y, King GD, Muhammad AK, et al. Engineering the brain tumor microenvironment enhances the efficacy of dendritic cell vaccination: implications for clinical trial design. Clin Cancer Res. 2011;17(14):4705–4718.
   PubMed Web of Science ®Google Scholar
• Kamran N, Kadiyala P, Saxena M, et al. Immunosuppressive myeloid cells’ blockade in the glioma microenvironment enhances the efficacy of immune-stimulatory gene therapy. Mol Ther. 2016. DOI:10.1016/j.ymthe.2016.10.003.
   Web of Science ®Google Scholar
• Rampling R, Peoples S, Mulholland PJ, et al. A cancer research UK first time in human phase I trial of IMA950 (novel multipeptide therapeutic vaccine) in patients with newly diagnosed glioblastoma. Clin Cancer Res. 2016;22(19):4776.
   PubMed Web of Science ®Google Scholar
• Narusawa M, Inoue H, Sakamoto C, et al. TLR7 ligand augments GM-CSF-initiated antitumor immunity through activation of plasmacytoid dendritic cells. Cancer Immuno Res. 2014;2(6):568–580.
   PubMed Web of Science ®Google Scholar
• Ohkuri T, Ghosh A, Kosaka A, et al. Protective role of STING against gliomagenesis: rational use of STING agonist in anti-glioma immunotherapy. Oncoimmunology. 2015;4(4):e999523.
   PubMed Web of Science ®Google Scholar
• Araki K, Turner AP, Shaffer VO, et al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009;460(7251):108–112.
   PubMed Web of Science ®Google Scholar
• Wang Y, Wang XY, Subjeck JR, et al. Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines. Br J Cancer. 2011;104(4):643–652.
   PubMed Web of Science ®Google Scholar
• Mineharu Y, Kamran N, Lowenstein PR, et al. Blockade of mTOR signaling via rapamycin combined with immunotherapy augments antiglioma cytotoxic and memory T-cell functions. Mol Cancer Ther. 2014;13(12):3024–3036.
   PubMed Web of Science ®Google Scholar
• Chaoul N, Fayolle C, Desrues B, et al. Rapamycin impairs antitumor CD8+ T-cell responses and vaccine-induced tumor eradication. Cancer Res. 2015;75(16):3279–3291.
   PubMed Web of Science ®Google 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.
   PubMed Web of Science ®Google Scholar
• Pellegatta S, Valletta L, Corbetta C, et al. Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma. Acta Neuropathol Commun. 2015;3:4.
   PubMed Web of Science ®Google Scholar
• Karbach J, Gnjatic S, Bender A, et al. Tumor-reactive CD8+ T-cell responses after vaccination with NY-ESO-1 peptide, CpG 7909 and Montanide ISA-51: association with survival. Int J Cancer. 2010;126(4):909–918.
   PubMed Web of Science ®Google Scholar
• Kostic A, Mihailovic D, Veselinovic S, et al. Tumor size and karyometric variables in brain astrocytoma. J BUON. 2009;14(3):473–477.
   PubMed Web of Science ®Google Scholar
• Markovic SN, Suman VJ, Ingle JN, et al. Peptide vaccination of patients with metastatic melanoma: improved clinical outcome in patients demonstrating effective immunization. Am J Clin Oncol. 2006;29(4):352–360.
   PubMed Web of Science ®Google Scholar
• Park MY, Kim CH, Sohn HJ, et al. The optimal interval for dendritic cell vaccination following adoptive T cell transfer is important for boosting potent anti-tumor immunity. Vaccine. 2007;25(42):7322–7330.
   PubMed Web of Science ®Google Scholar
• Tamai H, Watanabe S, Zheng R, et al. Effective treatment of spontaneous metastases derived from a poorly immunogenic murine mammary carcinoma by combined dendritic-tumor hybrid vaccination and adoptive transfer of sensitized T cells. Clin Immunol. 2008;127(1):66–77.
   PubMed Web of Science ®Google Scholar
• Song S, Zhang K, You H, et al. Significant anti-tumour activity of adoptively transferred T cells elicited by intratumoral dendritic cell vaccine injection through enhancing the ratio of CD8(+) T cell/regulatory T cells in tumour. Clin Exp Immunol. 2010;162(1):75–83.
   PubMed Web of Science ®Google Scholar
• Poschke I, Lovgren T, Adamson L, et al. A phase I clinical trial combining dendritic cell vaccination with adoptive T cell transfer in patients with stage IV melanoma. Cancer Immunol Immunother: CII. 2014;63(10):1061–1071.
   PubMed Web of Science ®Google Scholar
• Baker GJ, Yadav VN, Motsch S, et al. Mechanisms of glioma formation: iterative perivascular glioma growth and invasion leads to tumor progression, VEGF-independent vascularization, and resistance to antiangiogenic therapy. Neoplasia. 2014;16(7):543–561.
   PubMed Web of Science ®Google Scholar
• Khasraw M, Ameratunga MS, Grant R, et al. Antiangiogenic therapy for high-grade glioma. Cochrane Database Syst Rev. 2014;9:CD008218.
   Google Scholar
• Zhang B, Bowerman NA, Salama JK, et al. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 2007;204(1):49–55.
   PubMed Web of Science ®Google Scholar
• Li B, Lalani AS, Harding TC, et al. Vascular endothelial growth factor blockade reduces intratumoral regulatory T cells and enhances the efficacy of a GM-CSF-secreting cancer immunotherapy. Clin Cancer Res. 2006;12(22):6808–6816.
   PubMed Web of Science ®Google Scholar
• Bloch O, Crane CA, Fuks Y, et al. Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial. Neuro Oncol. 2014;16(2):274–279.
   PubMed Web of Science ®Google Scholar
• Sengupta S, Marrinan J, Frishman C, et al. Impact of temozolomide on immune response during malignant glioma chemotherapy. Clin Dev Immunol. 2012;2012:831090.
   PubMed Web of Science ®Google Scholar
• Sanchez-Perez L, Suryadevara CM, Choi BD, et al. Leveraging chemotherapy-induced lymphopenia to potentiate cancer immunotherapy. Oncoimmunology. 2014;3(7):e944054.
   PubMed Web of Science ®Google Scholar
• Sanchez-Perez LA, Choi BD, Archer GE, et al. Myeloablative temozolomide enhances CD8(+) T-cell responses to vaccine and is required for efficacy against brain tumors in mice. PLoS One. 2013;8(3):e59082.
   PubMed Web of Science ®Google Scholar
• Sampson JH, Aldape KD, Archer GE, et al. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Neuro Oncol. 2011;13(3):324–333.
   PubMed Web of Science ®Google Scholar
• Lamb LS, Bowersock J, Dasgupta A, et al. Engineered drug resistant γδ T cells kill glioblastoma cell lines during a chemotherapy challenge: a strategy for combining chemo- and immunotherapy. PLoS One. 2013;8(1):e51805.
   PubMed Web of Science ®Google Scholar
• Adair JE, Beard BC, Trobridge GD, et al. Extended survival of glioblastoma patients after chemoprotective HSC gene therapy. Sci Transl Med. 2012;4(133):133ra57–33ra57.
   PubMed Web of Science ®Google Scholar
• Adair JE, Johnston SK, Mrugala MM, et al. Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients. J Clin Invest. 2014;124(9):4082–4092.
   PubMed Web of Science ®Google Scholar
• Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14(9):642–662.
   PubMed Web of Science ®Google Scholar
• Brown MC, Gromeier M. Oncolytic immunotherapy through tumor-specific translation and cytotoxicity of poliovirus. Discov Med. 2015;19(106):359–365.
   PubMed Web of Science ®Google Scholar
• Brown MC, Dobrikova EY, Dobrikov MI, et al. Oncolytic polio virotherapy of cancer. Cancer. 2014;120(21):3277–3286.
   PubMed Web of Science ®Google Scholar
• Patel AP. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science (New York, NY). 2014;344(6190):1396–1401.
   Google Scholar
• Berghoff AS, Kiesel B, Widhalm G, et al. Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro Oncol. 2015;17(8):1064–1075.
   PubMed Web of Science ®Google Scholar
• Ohgaki HH. The definition of primary and secondary glioblastoma. Clinical Cancer Research. 2013;19(4):764–772.
   PubMed Web of Science ®Google Scholar
• Crespo J, Sun H, Welling TH, et al. T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment. Curr Opin Immunol. 2013;25(2):214–221.
   PubMed Web of Science ®Google Scholar