Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives
Abstract
:Simple Summary
Abstract
1. Introduction
2. Medulloblastoma Classification
3. Immunotherapy in Medulloblastoma
3.1. Immune Checkpoint Inhibitors
3.2. PD-1/PD-L1 Immune Checkpoints
3.3. B7 Family Immune Checkpoints
3.4. IDO Immune Checkpoints
3.5. CD40 Immune Checkpoints
3.6. Tim-3 and Tim-4 Immune Checkpoints
3.7. CAR T-Cell Therapy for Medulloblastoma
4. Challenges of Immunotherapy in Medulloblastoma
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Ostrom, Q.T.; Cioffi, G.; Gittleman, H.; Patil, N.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012–2016. J. Neurooncol. 2019, 21, v1–v100. [Google Scholar] [CrossRef]
- Van Ommeren, R.; Garzia, L.; Holgado, B.L.; Ramaswamy, V.; Taylor, M.D. The molecular biology of medulloblastoma metastasis. Brain Pathol. 2019, 30, 691–702. [Google Scholar] [CrossRef]
- Taylor, M.D.; Northcott, P.A.; Korshunov, A.; Remke, M.; Cho, Y.-J.; Clifford, S.C.; Eberhart, C.G.; Parsons, D.W.; Rutkowski, S.; Gajjar, A.; et al. Molecular subgroups of medulloblastoma: The current consensus. Acta Neuropathol. 2011, 123, 465–472. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Northcott, P.A.; Buchhalter, I.; Morrissy, A.S.; Hovestadt, V.; Weischenfeldt, J.; Ehrenberger, T.; Gröbner, S.; Segura-Wang, M.; Zichner, T.; Rudneva, V.A.; et al. The whole-genome landscape of medulloblastoma subtypes. Nature 2017, 547, 311–317. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Louis, D.N.; Perry, A.; Reifenberger, G.; von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol. 2016, 131, 803–820. [Google Scholar] [CrossRef] [Green Version]
- Wilne, S.; Collier, J.; Kennedy, C.; Koller, K.; Grundy, R.; Walker, D. Presentation of childhood CNS tumours: A systematic review and meta-analysis. Lancet Oncol. 2007, 8, 685–695. [Google Scholar] [CrossRef]
- Vinchon, M.; Leblond, P. Medulloblastoma: Clinical presentation. Neurochirurgie 2019, 67, 23–27. [Google Scholar] [CrossRef] [PubMed]
- Zapotocky, M.; Mata-Mbemba, D.; Sumerauer, D.; Liby, P.; Lassaletta, A.; Zamecnik, J.; Krsková, L.; Kyncl, M.; Stary, J.; Laughlin, S.; et al. Differential patterns of metastatic dissemination across medulloblastoma subgroups. J. Neurosurg. Pediatr. 2018, 21, 145–152. [Google Scholar] [CrossRef] [PubMed]
- Udaka, Y.T.; Packer, R.J. Pediatric Brain Tumors. Neurol. Clin. 2018, 36, 533–556. [Google Scholar] [CrossRef]
- Minn, A.Y.; Pollock, B.H.; Garzarella, L.; Dahl, G.V.; Kun, L.E.; Ducore, J.M.; Shibata, A.; Kepner, J.; Fisher, P. Surveillance Neuroimaging to Detect Relapse in Childhood Brain Tumors: A Pediatric Oncology Group Study. J. Clin. Oncol. 2001, 19, 4135–4140. [Google Scholar] [CrossRef] [PubMed]
- Robertson, P.L.; Muraszko, K.M.; Holmes, E.J.; Sposto, R.; Packer, R.J.; Gajjar, A.; Dias, M.S.; Allen, J.C. Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: A prospective study by the Children’s Oncology Group. J. Neurosurg. Pediatr. 2006, 105, 444–451. [Google Scholar] [CrossRef] [PubMed]
- Glass, J.; Ogg, R.J.; Hyun, J.W.; Harreld, J.H.; E Schreiber, J.; Palmer, S.L.; Li, Y.; Gajjar, A.J.; Reddick, W. Disrupted development and integrity of frontal white matter in patients treated for pediatric medulloblastoma. J. Neurooncol. 2017, 19, 1408–1418. [Google Scholar] [CrossRef] [Green Version]
- Mulhern, R.K.; Reddick, W.E.; Palmer, S.L.; Glass, J.O.; Elkin, T.D.; Kun, L.E.; Taylor, J.; Langston, J.; Gajjar, A. Neurocognitive deficits in medulloblastoma survivors and white matter loss. Ann. Neurol. 1999, 46, 834–841. [Google Scholar] [CrossRef]
- Esfahani, K.; Roudaia, L.; Buhlaiga, N.; Del Rincon, S.; Papneja, N.; Miller, W. A Review of Cancer Immunotherapy: From the Past, to the Present, to the Future. Curr. Oncol. 2020, 27, 87–97. [Google Scholar] [CrossRef] [PubMed]
- Sondak, V.K.; Smalley, K.; Kudchadkar, R.; Grippon, S.; Kirkpatrick, P. Ipilimumab. Nat. Rev. Drug Discov. 2011, 10, 411–412. [Google Scholar] [CrossRef]
- Thompson, M.C.; Fuller, C.; Hogg, T.L.; Dalton, J.; Finkelstein, D.; Lau, C.C.; Chintagumpala, M.; Adesina, A.; Ashley, D.M.; Kellie, S.J.; et al. Genomics Identifies Medulloblastoma Subgroups That Are Enriched for Specific Genetic Alterations. J. Clin. Oncol. 2006, 24, 1924–1931. [Google Scholar] [CrossRef]
- Pham, C.D.; Flores, C.; Yang, C.; Pinheiro, E.M.; Yearley, J.H.; Sayour, E.J.; Pei, Y.; Moore, C.; McLendon, R.E.; Huang, J.; et al. Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma. Clin. Cancer Res. 2015, 22, 582–595. [Google Scholar] [CrossRef] [Green Version]
- Martin, A.M.; Nirschl, C.J.; Polanczyk, M.J.; Bell, W.R.; Nirschl, T.R.; Harris-Bookman, S.; Phallen, J.; Hicks, J.; Martinez, D.; Ogurtsova, A.; et al. PD-L1 expression in medulloblastoma: An evaluation by subgroup. Oncotarget 2018, 9, 19177–19191. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bockmayr, M.; Mohme, M.; Klauschen, F.; Winkler, B.; Budczies, J.; Rutkowski, S.; Schüller, U. Subgroup-specific immune and stromal microenvironment in medulloblastoma. Oncoimmunology 2018, 7, e1462430. [Google Scholar] [CrossRef] [Green Version]
- Purvis, I.J.; Avilala, J.; Guda, M.R.; Venkataraman, S.; Vibhakar, R.; Tsung, A.J.; Velpula, K.K.; Asuthkar, S. Role of MYC-miR-29-B7-H3 in Medulloblastoma Growth and Angiogenesis. J. Clin. Med. 2019, 8, 1158. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kanchan, R.K.; Perumal, N.; Atri, P.; Venkata, R.C.; Thapa, I.; Klinkebiel, D.L.; Donson, A.M.; Perry, D.; Punsoni, M.; Talmon, G.A.; et al. MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3). Brain Pathol. 2020, 30, 732–745. [Google Scholar] [CrossRef]
- Northcott, P.A.; Dubuc, A.M.; Pfister, S.; Taylor, M.D. Molecular subgroups of medulloblastoma. Expert Rev. Neurother. 2012, 12, 871–884. [Google Scholar] [CrossRef] [Green Version]
- Gibson, P.; Tong, Y.; Robinson, G.; Thompson, M.C.; Currle, D.S.; Eden, C.; Kranenburg, T.; Hogg, T.; Poppleton, H.; Martin, J.; et al. Subtypes of medulloblastoma have distinct developmental origins. Nature 2010, 468, 1095–1099. [Google Scholar] [CrossRef]
- Northcott, P.A.; Robinson, G.W.; Kratz, C.P.; Mabbott, D.J.; Pomeroy, S.L.; Clifford, S.C.; Rutkowski, S.; Ellison, D.W.; Malkin, D.; Taylor, M.D.; et al. Medulloblastoma. Nat. Rev. Dis. Prim. 2019, 5, 11. [Google Scholar] [CrossRef]
- Schüller, U.; Heine, V.M.; Mao, J.; Kho, A.T.; Dillon, A.K.; Han, Y.-G.; Huillard, E.; Sun, T.; Ligon, A.H.; Qian, Y.; et al. Acquisition of Granule Neuron Precursor Identity Is a Critical Determinant of Progenitor Cell Competence to Form Shh-Induced Medulloblastoma. Cancer Cell 2008, 14, 123–134. [Google Scholar] [CrossRef] [Green Version]
- Hooper, C.M.; Hawes, S.M.; Kees, U.R.; Gottardo, N.; Dallas, P.B. Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis. PLoS ONE 2014, 9, e112909. [Google Scholar] [CrossRef] [Green Version]
- Lin, C.Y.; Erkek, S.; Tong, Y.; Yin, L.; Federation, A.J.; Zapatka, M.; Haldipur, P.; Kawauchi, D.; Risch, T.; Warnatz, H.-J.; et al. Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature 2016, 530, 57–62. [Google Scholar] [CrossRef] [Green Version]
- Kumar, V.; Kumar, V.; McGuire, T.; Coulter, D.W.; Sharp, J.G.; Mahato, R.I. Challenges and Recent Advances in Medulloblastoma Therapy. Trends Pharmacol. Sci. 2017, 38, 1061–1084. [Google Scholar] [CrossRef] [PubMed]
- Cavalli, F.M.; Remke, M.; Rampasek, L.; Peacock, J.; Shih, D.J.H.; Luu, B.; Garzia, L.; Torchia, J.; Nor, C.; Morrissy, S.; et al. Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell 2017, 31, 737–754.e6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pfaff, E.; Remke, M.; Sturm, D.; Benner, A.; Witt, H.; Milde, T.; von Bueren, A.O.; Wittmann, A.; Schöttler, A.; Jorch, N.; et al. TP53 Mutation Is Frequently Associated with CTNNB1 Mutation or MYCN Amplification and Is Compatible with Long-Term Survival in Medulloblastoma. J. Clin. Oncol. 2010, 28, 5188–5196. [Google Scholar] [CrossRef] [PubMed]
- Robinson, G.; Parker, M.; Kranenburg, T.; Lu, C.; Chen, X.; Ding, L.; Phoenix, T.N.; Hedlund, E.; Wei, L.; Zhu, X.; et al. Novel mutations target distinct subgroups of medulloblastoma. Nature 2012, 488, 43–48. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pugh, T.; Weeraratne, S.D.; Archer, T.C.; Krummel, D.A.P.; Auclair, D.; Bochicchio, J.; Carneiro, M.O.; Carter, S.L.; Cibulskis, K.; Erlich, R.L.; et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 2012, 488, 106–110. [Google Scholar] [CrossRef] [PubMed]
- Northcott, P.A.; Shih, D.J.H.; Peacock, J.; Garzia, L.; Morrissy, A.S.; Zichner, T.; Stütz, A.M.; Korshunov, A.; Reimand, J.; Schumacher, S.E.; et al. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 2012, 488, 49–56. [Google Scholar] [CrossRef] [PubMed]
- Boulay, G.; Awad, M.E.; Riggi, N.; Archer, T.C.; Iyer, S.; Boonseng, W.E.; Rossetti, N.E.; Naigles, B.; Rengarajan, S.; Volorio, A.; et al. OTX2 Activity at Distal Regulatory Elements Shapes the Chromatin Landscape of Group 3 Medulloblastoma. Cancer Discov. 2017, 7, 288–301. [Google Scholar] [CrossRef] [Green Version]
- Northcott, P.A.; Lee, C.; Zichner, T.; Stütz, A.M.; Erkek, S.; Kawauchi, D.; Shih, D.J.H.; Hovestadt, V.; Zapatka, M.; Sturm, D.; et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 2014, 511, 428–434. [Google Scholar] [CrossRef]
- Ramaswamy, V.; Remke, M.; Bouffet, E.; Bailey, S.; Clifford, S.C.; Doz, F.; Kool, M.; Dufour, C.; Vassal, G.; Milde, T.; et al. Risk stratification of childhood medulloblastoma in the molecular era: The current consensus. Acta Neuropathol. 2016, 131, 821–831. [Google Scholar] [CrossRef] [Green Version]
- Northcott, P.A.; Hielscher, T.; Dubuc, A.; Mack, S.C.; Shih, D.J.H.; Remke, M.; Al-Halabi, H.; Albrecht, S.; Jabado, N.; Eberhart, C.G.; et al. Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathol. 2011, 122, 231–240. [Google Scholar] [CrossRef]
- Yang, Z.-J.; Ellis, T.; Markant, S.L.; Read, T.-A.; Kessler, J.D.; Bourboulas, M.; Schüller, U.; Machold, R.; Fishell, G.; Rowitch, D.H.; et al. Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells. Cancer Cell 2008, 14, 135–145. [Google Scholar] [CrossRef] [Green Version]
- Ingham, P.W.; McMahon, A.P. Hedgehog Signaling in Animal Development: Paradigms and Principles. Genes Dev. 2001, 15, 3059–3087. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhukova, N.; Ramaswamy, V.; Remke, M.; Pfaff, E.; Shih, D.J.H.; Martin, D.C.; Castelo-Branco, P.; Baskin, B.; Ray, P.N.; Bouffet, E.; et al. Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma. J. Clin. Oncol. 2013, 31, 2927–2935. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tao, R.; Murad, N.; Xu, Z.; Zhang, P.; Okonechnikov, K.; Kool, M.; Hinojosa, S.R.; Lazarski, C.; Zheng, P.; Liu, Y.; et al. MYC Drives Group 3 Medulloblastoma through Transformation of Sox2+ Astrocyte Progenitor Cells. Cancer Res. 2019, 79, 1967–1980. [Google Scholar] [CrossRef] [Green Version]
- Gröbner, S.N.; Project, I.P.-S.; Worst, B.C.; Weischenfeldt, J.; Buchhalter, I.; Kleinheinz, K.; Rudneva, V.A.; Johann, P.D.; Balasubramanian, G.P.; Segura-Wang, M.; et al. The landscape of genomic alterations across childhood cancers. Nature 2018, 555, 321–327. [Google Scholar] [CrossRef] [Green Version]
- Lawrence, M.S.; Stojanov, P.; Polak, P.; Kryukov, G.; Cibulskis, K.; Sivachenko, A.; Carter, S.L.; Stewart, C.; Mermel, C.; Roberts, S.A.; et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013, 499, 214–218. [Google Scholar] [CrossRef]
- Kabir, T.F.; Kunos, C.A.; Villano, J.L.; Chauhan, A. Immunotherapy for Medulloblastoma: Current Perspectives. ImmunoTargets Ther. 2020, 9, 57–77. [Google Scholar] [CrossRef] [Green Version]
- Hemminki, O.; Dos Santos, J.M.; Hemminki, A. Oncolytic viruses for cancer immunotherapy. J. Hematol. Oncol. 2020, 13, 84. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.; Liu, F. Advances and potential pitfalls of oncolytic viruses expressing immunomodulatory transgene therapy for malignant gliomas. Cell Death Dis. 2020, 11, 485. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stanford, M.M.; Breitbach, C.J.; Bell, J.C.; McFadden, G. Innate Immunity, Tumor Microenvironment and Oncolytic Virus Therapy: Friends or Foes? Curr. Opin. Mol. Ther. 2008, 10, 32–37. [Google Scholar] [PubMed]
- Sayour, E.J.; Mitchell, D.A. Immunotherapy for Pediatric Brain Tumors. Brain Sci. 2017, 7, 137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jähnisch, H.; Füssel, S.; Kiessling, A.; Wehner, R.; Zastrow, S.; Bachmann, M.; Rieber, E.P.; Wirth, M.P.; Schmitz, M. Dendritic Cell-Based Immunotherapy for Prostate Cancer. Clin. Dev. Immunol. 2010, 2010, 517493. [Google Scholar] [CrossRef] [PubMed]
- McNamara, M.A.; Nair, S.K.; Holl, E.K. RNA-Based Vaccines in Cancer Immunotherapy. J. Immunol. Res. 2015, 2015, 794528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jahanafrooz, Z.; Baradaran, B.; Mosafer, J.; Hashemzaei, M.; Rezaei, T.; Mokhtarzadeh, A.; Hamblin, M.R. Comparison of DNA and mRNA vaccines against cancer. Drug Discov. Today 2019, 25, 552–560. [Google Scholar] [CrossRef] [PubMed]
- Weller, M.; Butowski, N.; Tran, D.D.; Recht, L.D.; Lim, M.; Hirte, H.; Ashby, L.; Mechtler, L.; A Goldlust, S.; Iwamoto, F.; et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): A randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017, 18, 1373–1385. [Google Scholar] [CrossRef] [Green Version]
- Sharpe, A.H. Introduction to checkpoint inhibitors and cancer immunotherapy. Immunol. Rev. 2017, 276, 5–8. [Google Scholar] [CrossRef] [Green Version]
- Vinay, D.S.; Ryan, E.P.; Pawelec, G.; Talib, W.; Stagg, J.; Elkord, E.; Lichtor, T.; Decker, W.K.; Whelan, R.L.; Kumara, H.S.; et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin. Cancer Biol. 2015, 35, S185–S198. [Google Scholar] [CrossRef] [PubMed]
- Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12, 252–264. [Google Scholar] [CrossRef] [Green Version]
- Wei, S.C.; Duffy, C.R.; Allison, J.P. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov. 2018, 8, 1069–1086. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vaddepally, R.K.; Kharel, P.; Pandey, R.; Garje, R.; Chandra, A.B. Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence. Cancers 2020, 12, 738. [Google Scholar] [CrossRef] [Green Version]
- Ueno, M.; Chiba, Y.; Murakami, R.; Matsumoto, K.; Kawauchi, M.; Fujihara, R. Blood–Brain barrier and blood–cerebrospinal fluid barrier in normal and pathological conditions. Brain Tumor Pathol. 2016, 33, 89–96. [Google Scholar] [CrossRef] [PubMed]
- Pardridge, W.M. Drug Transport across the Blood–Brain Barrier. Br. J. Pharmacol. 2012, 32, 1959–1972. [Google Scholar] [CrossRef]
- Wang, S.S.; Bandopadhayay, P.; Jenkins, M.R. Towards Immunotherapy for Pediatric Brain Tumors. Trends Immunol. 2019, 40, 748–761. [Google Scholar] [CrossRef] [Green Version]
- Friedlaender, A.; Addeo, A.; Banna, G. New emerging targets in cancer immunotherapy: The role of TIM3. ESMO Open 2019, 4, e000497. [Google Scholar] [CrossRef] [Green Version]
- Moon, Y.W.; Hajjar, J.; Hwu, P.; Naing, A. Targeting the indoleamine 2,3-dioxygenase pathway in cancer. J. Immunother. Cancer 2015, 3, 51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vonderheide, R.H. CD40 Agonist Antibodies in Cancer Immunotherapy. Annu. Rev. Med. 2020, 71, 47–58. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Keir, M.E.; Butte, M.; Freeman, G.J.; Sharpe, A.H. PD-1 and Its Ligands in Tolerance and Immunity. Annu. Rev. Immunol. 2008, 26, 677–704. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiang, X.; Wang, J.; Deng, X.; Xiong, F.; Ge, J.; Xiang, B.; Wu, X.; Ma, J.; Zhou, M.; Li, X.; et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol. Cancer 2019, 18, 10. [Google Scholar] [CrossRef] [Green Version]
- Vermeulen, J.F.; Van Hecke, W.; Adriaansen, E.J.M.; Jansen, M.K.; Bouma, R.G.; Hidalgo, J.V.; Fisch, P.; Broekhuizen, R.; Spliet, W.G.M.; Kool, M.; et al. Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma. Oncoimmunology 2017, 7, e1398877. [Google Scholar] [CrossRef] [PubMed]
- Majzner, R.G.; Simon, J.S.; Grosso, J.F.; Martinez, D.; Pawel, B.R.; Santi, M.; Merchant, M.S.; Geoerger, B.; Hezam, I.; Marty, V.; et al. Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues. Cancer 2017, 123, 3807–3815. [Google Scholar] [CrossRef] [Green Version]
- Omuro, A.; Vlahovic, G.; Lim, M.; Sahebjam, S.; Baehring, J.; Cloughesy, T.; Voloschin, A.; Ramkissoon, S.H.; Ligon, K.L.; Latek, R.; et al. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. J. Neurooncol. 2017, 20, 674–686. [Google Scholar] [CrossRef]
- Murata, D.; Mineharu, Y.; Arakawa, Y.; Liu, B.; Tanji, M.; Yamaguchi, M.; Fujimoto, K.-I.; Fukui, N.; Terada, Y.; Yokogawa, R.; et al. High programmed cell death 1 ligand–1 expression: Association with CD8+ T-cell infiltration and poor prognosis in human medulloblastoma. J. Neurosurg. 2018, 128, 710–716. [Google Scholar] [CrossRef] [Green Version]
- Allen, F.; Dorand, R.D.; Rauhe, P.; Petrosiute, A.; Huang, A.Y. The Efficacy of PD-L1 Blockade on PD-L1 Negative Medulloblastoma Is Dependent on Timing and the Tumor Microenvironment. J. Immunol. 2018, 200 (Suppl. 1), 178.14. [Google Scholar]
- Messenheimer, D.J.; Jensen, S.M.; Afentoulis, M.E.; Wegmann, K.W.; Feng, Z.; Friedman, D.J.; Gough, M.; Urba, W.J.; Fox, B.A. Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40. Clin. Cancer Res. 2017, 23, 6165–6177. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Buchan, S.L.; Manzo, T.; Flutter, B.; Rogel, A.; Edwards, N.; Zhang, L.; Sivakumaran-Nguyen, S.; Ghorashian, S.; Carpenter, B.; Bennett, C.L.; et al. OX40- and CD27-Mediated Costimulation Synergizes with Anti–PD-L1 Blockade by Forcing Exhausted CD8+ T Cells to Exit Quiescence. J. Immunol. 2014, 194, 125–133. [Google Scholar] [CrossRef] [Green Version]
- Gattinoni, L.; Klebanoff, C.; Palmer, D.; Wrzesinski, C.; Kerstann, K.W.; Yu, Z.; Finkelstein, S.E.; Theoret, M.R.; Rosenberg, S.A.; Restifo, N.P. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J. Clin. Investig. 2005, 115, 1616–1626. [Google Scholar] [CrossRef]
- Margol, A.S.; Robison, N.J.; Gnanachandran, J.; Hung, L.T.; Kennedy, R.J.; Vali, M.; Dhall, G.; Finlay, J.L.; Epstein, A.; Krieger, M.D.; et al. Tumor-Associated Macrophages in SHH Subgroup of Medulloblastomas. Clin. Cancer Res. 2014, 21, 1457–1465. [Google Scholar] [CrossRef] [Green Version]
- Gabrilovich, D.I.; Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 2009, 9, 162–174. [Google Scholar] [CrossRef] [PubMed]
- Pollard, J.W. Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer 2004, 4, 71–78. [Google Scholar] [CrossRef]
- Xu-Monette, Z.Y.; Zhang, M.; Li, J.; Young, K.H. PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response? Front. Immunol. 2017, 8, 1597. [Google Scholar] [CrossRef] [Green Version]
- Brahmer, J.R.; Reckamp, K.; Baas, P.; Crinò, L.; Eberhardt, W.E.; Poddubskaya, E.; Antonia, S.; Pluzanski, A.; Vokes, E.E.; Holgado, E.; et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2015, 373, 123–135. [Google Scholar] [CrossRef] [Green Version]
- Chen, P.-L.; Roh, W.; Reuben, A.; Cooper, Z.; Spencer, C.N.; Prieto, P.A.; Miller, J.P.; Bassett, R.L.; Gopalakrishnan, V.; Wani, K.; et al. Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade. Cancer Discov. 2016, 6, 827–837. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cherkassky, L.; Morello, A.; Villena-Vargas, J.; Feng, Y.; Dimitrov, D.S.; Jones, D.R.; Sadelain, M.; Adusumilli, P.S. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J. Clin. Investig. 2016, 126, 3130–3144. [Google Scholar] [CrossRef] [Green Version]
- Fourcade, J.; Sun, Z.; Benallaoua, M.; Guillaume, P.; Luescher, I.F.; Sander, C.; Kirkwood, J.M.; Kuchroo, V.; Zarour, H.M. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen–specific CD8+ T cell dysfunction in melanoma patients. J. Exp. Med. 2010, 207, 2175–2186. [Google Scholar] [CrossRef]
- Holmgaard, R.B.; Zamarin, D.; Munn, D.; Wolchok, J.D.; Allison, J.P. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J. Exp. Med. 2013, 210, 1389–1402. [Google Scholar] [CrossRef] [PubMed]
- Loo, D.; Alderson, R.F.; Chen, F.Z.; Huang, L.; Zhang, W.; Gorlatov, S.; Burke, S.; Ciccarone, V.; Li, H.; Yang, Y.; et al. Development of an Fc-Enhanced Anti–B7-H3 Monoclonal Antibody with Potent Antitumor Activity. Clin. Cancer Res. 2012, 18, 3834–3845. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Souweidane, M.M.; Kramer, K.; Pandit-Taskar, N.; Zhou, Z.; Haque, S.; Zanzonico, P.; Carrasquillo, J.; Lyashchenko, S.K.; Thakur, S.; Donzelli, M.; et al. Convection-enhanced delivery for diffuse intrinsic pontine glioma: A single-centre, dose-escalation, phase 1 trial. Lancet Oncol. 2018, 19, 1040–1050. [Google Scholar] [CrossRef]
- Gregorio, A.; Corrias, M.V.; Castriconi, R.; Dondero, A.; Mosconi, M.; Gambini, C.; Moretta, A.; Moretta, L.; Bottino, C. Small round blue cell tumours: Diagnostic and prognostic usefulness of the expression of B7-H3 surface molecule. Histopathology 2008, 53, 73–80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kwon, J.J.; Factora, T.D.; Dey, S.; Kota, J. A Systematic Review of miR-29 in Cancer. Mol. Ther. Oncolytics 2018, 12, 173–194. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, X.; Zhao, X.; Fiskus, W.; Lin, J.; Lwin, T.; Rao, R.; Zhang, Y.; Chan, J.C.; Fu, K.; Marquez, V.E.; et al. Coordinated Silencing of MYC-Mediated miR-29 by HDAC3 and EZH2 as a Therapeutic Target of Histone Modification in Aggressive B-Cell Lymphomas. Cancer Cell 2012, 22, 506–523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, H.; Cheung, I.Y.; Guo, H.-F.; Cheung, N.-K.V. MicroRNA miR-29 Modulates Expression of Immunoinhibitory Molecule B7-H3: Potential Implications for Immune Based Therapy of Human Solid Tumors. Cancer Res. 2009, 69, 6275–6281. [Google Scholar] [CrossRef] [Green Version]
- Purvis, I.J.; Velpula, K.K.; Guda, M.R.; Nguyen, D.; Tsung, A.J.; Asuthkar, S. B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role. Int. J. Mol. Sci. 2020, 21, 7050. [Google Scholar] [CrossRef]
- Epple, L.M.; Griffiths, S.G.; Dechkovskaia, A.M.; Dusto, N.L.; White, J.; Ouellette, R.J.; Anchordoquy, T.J.; Bemis, L.; Graner, M.W. Medulloblastoma Exosome Proteomics Yield Functional Roles for Extracellular Vesicles. PLoS ONE 2012, 7, e42064. [Google Scholar] [CrossRef] [Green Version]
- Ciregia, F.; Urbani, A.; Palmisano, G. Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases. Front. Mol. Neurosci. 2017, 10, 276. [Google Scholar] [CrossRef] [Green Version]
- Holmgaard, R.B.; Zamarin, D.; Li, Y.; Gasmi, B.; Munn, D.; Allison, J.; Merghoub, T.; Wolchok, J.D. Tumor-Expressed IDO Recruits and Activates MDSCs in a Treg-Dependent Manner. Cell Rep. 2015, 13, 412–424. [Google Scholar] [CrossRef] [Green Version]
- Opitz, C.A.; Litzenburger, U.M.; Sahm, F.; Ott, M.; Tritschler, I.; Trump, S.; Schumacher, T.; Jestaedt, L.; Schrenk, D.; Weller, M.; et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 2011, 478, 197–203. [Google Scholar] [CrossRef]
- Ozawa, Y.; Yamamuro, S.; Sano, E.; Tatsuoka, J.; Hanashima, Y.; Yoshimura, S.; Sumi, K.; Hara, H.; Nakayama, T.; Suzuki, Y.; et al. Indoleamine 2,3-dioxygenase 1 is highly expressed in glioma stem cells. Biochem. Biophys. Res. Commun. 2020, 524, 723–729. [Google Scholar] [CrossRef] [PubMed]
- Folgiero, V.; Miele, E.; Carai, A.; Ferretti, E.; Alfano, V.; Po, A.; Bertaina, V.; Goffredo, B.; Benedetti, M.C.; Camassei, F.D.; et al. IDO1 involvement in mTOR pathway: A molecular mechanism of resistance to mTOR targeting in medulloblastoma. Oncotarget 2016, 7, 52900–52911. [Google Scholar] [CrossRef] [Green Version]
- Zhang, J.; Wang, T. Immune cell landscape and immunotherapy of medulloblastoma. Pediatr. Investig. 2021. [Google Scholar] [CrossRef]
- Li, M.; Bolduc, A.R.; Hoda, N.; Gamble, D.N.; Dolisca, S.-B.; Bolduc, A.K.; Hoang, K.; Ashley, C.; McCall, D.; Rojiani, A.M.; et al. The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma. J. Immunother. Cancer 2014, 2, 21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vonderheide, R.H. Prospect of Targeting the CD40 Pathway for Cancer Therapy. Clin. Cancer Res. 2007, 13, 1083–1088. [Google Scholar] [CrossRef] [Green Version]
- Xie, F.; Shi, Q.; Wang, Q.; Ge, Y.; Chen, Y.; Zuo, J.; Gu, Y.; Deng, H.; Mao, H.; Hu, Z. CD40 is a regulator for vascular endothelial growth factor in the tumor microenvironment of glioma. J. Neuroimmunol. 2010, 222, 62–69. [Google Scholar] [CrossRef] [PubMed]
- Chonan, M.; Saito, R.; Shoji, T.; Shibahara, I.; Kanamori, M.; Sonoda, Y.; Watanabe, M.; Kikuchi, T.; Ishii, N.; Tominaga, T. CD40/CD40L expression correlates with the survival of patients with glioblastomas and an augmentation in CD40 signaling enhances the efficacy of vaccinations against glioma models. J. Neurooncol. 2015, 17, 1453–1462. [Google Scholar] [CrossRef] [Green Version]
- 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 Immunol. Immunother. 2014, 63, 847–857. [Google Scholar] [CrossRef] [Green Version]
- Derouazi, M.S.; di Berardino-Besson, W.; Belnoue, E.; Hoepner, S.; Walther, R.; Benkhoucha, M.; Teta, P.; Dufour, Y.J.; Maroun, C.Y.; Salazar, A.M.; et al. Novel Cell-Penetrating Peptide-Based Vaccine Induces Robust CD4+ and CD8+ T Cell–Mediated Antitumor Immunity. Cancer Res. 2015, 75, 3020–3031. [Google Scholar] [CrossRef] [Green Version]
- Van Hooren, L.; Vaccaro, A.; Ramachandran, M.; Vazaios, K.; Libard, S.; van de Walle, T.; Georganaki, M.; Huang, H.; Pietilä, I.; Lau, J.; et al. Agonistic CD40 Antibody Therapy Induces Tertiary Lymphoid Structures but Impairs the Response to Immune Checkpoint Blockade in Glioma. bioRxiv 2021. [Google Scholar] [CrossRef]
- Vonderheide, R.H.; Glennie, M.J. Agonistic CD40 Antibodies and Cancer Therapy. Clin. Cancer Res. 2013, 19, 1035–1043. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Anderson, A.C. Tim-3: An Emerging Target in the Cancer Immunotherapy Landscape. Cancer Immunol. Res. 2014, 2, 393–398. [Google Scholar] [CrossRef] [Green Version]
- Han, S.; Feng, S.; Xu, L.; Shi, W.; Wang, X.; Wang, H.; Yu, C.; Dong, T.; Xu, M.; Liang, G. Tim-3 on Peripheral CD4+ and CD8+ T Cells Is Involved in the Development of Glioma. DNA Cell Biol. 2014, 33, 245–250. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Liu, X.; Duan, Y.; Liu, Y.; Wang, H.; Lian, S.; Zhuang, G.; Fan, Y. Combined Blockade of T Cell Immunoglobulin and Mucin Domain 3 and Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Results in Durable Therapeutic Efficacy in Mice with Intracranial Gliomas. Med. Sci. Monit. 2017, 23, 3593–3602. [Google Scholar] [CrossRef] [Green Version]
- Xu, L.; Xiao, H.; Xu, M.; Zhou, C.; Yi, L.; Liang, H. Glioma-derived T Cell Immunoglobulin- and Mucin Domain-containing Molecule-4 (TIM4) Contributes to Tumor Tolerance. J. Biol. Chem. 2011, 286, 36694–36699. [Google Scholar] [CrossRef] [Green Version]
- Sampson, J.H.; Gunn, M.D.; Fecci, P.E.; Ashley, D.M. Brain immunology and immunotherapy in brain tumours. Nat. Rev. Cancer 2019, 20, 12–25. [Google Scholar] [CrossRef]
- Rosenberg, S.A.; Dudley, M.E. Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes. Proc. Natl. Acad. Sci. USA 2004, 101, 14639–14645. [Google Scholar] [CrossRef] [Green Version]
- Sadelain, M.; Brentjens, R.; Rivière, I. The Basic Principles of Chimeric Antigen Receptor Design. Cancer Discov. 2013, 3, 388–398. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Majzner, R.G.; Theruvath, J.L.; Nellan, A.; Heitzeneder, S.; Cui, Y.; Mount, C.W.; Rietberg, S.P.; Linde, M.H.; Xu, P.; Rota, C.; et al. CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Clin. Cancer Res. 2019, 25, 2560–2574. [Google Scholar] [CrossRef] [PubMed]
- Nellan, A.; Rota, C.; Majzner, R.; Lester-McCully, C.M.; Griesinger, A.M.; Levy, J.M.M.; Foreman, N.K.; Warren, K.E.; Lee, D.W. Durable regression of Medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. J. Immunother. Cancer 2018, 6, 30. [Google Scholar] [CrossRef] [Green Version]
- Ahmed, N.; Brawley, V.; Hegde, M.; Bielamowicz, K.; Kalra, M.; Landi, D.; Robertson, C.; Gray, T.L.; Diouf, O.; Wakefield, A.; et al. HER2-Specific Chimeric Antigen Receptor–Modified Virus-Specific T Cells for Progressive Glioblastoma. JAMA Oncol. 2017, 3, 1094–1101. [Google Scholar] [CrossRef] [PubMed]
- Orlando, D.; Miele, E.; De Angelis, B.; Guercio, M.; Boffa, I.; Sinibaldi, M.; Po, A.; Caruana, I.; Abballe, L.; Carai, A.; et al. Adoptive Immunotherapy Using PRAME-Specific T Cells in Medulloblastoma. Cancer Res. 2018, 78, 3337–3349. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ahmad, Z.; Jasnos, L.; Gil, V.; Howell, L.; Hallsworth, A.; Petrie, K.; Sawado, T.; Chesler, L. Molecular and In Vivo Characterization of Cancer-Propagating Cells Derived from MYCN-Dependent Medulloblastoma. PLoS ONE 2015, 10, e0119834. [Google Scholar] [CrossRef]
- Corno, D.; Pala, M.; Cominelli, M.; Cipelletti, B.; Leto, K.; Croci, L.; Barili, V.; Brandalise, F.; Melzi, R.; Di Gregorio, A.; et al. Gene Signatures Associated with Mouse Postnatal Hindbrain Neural Stem Cells and Medulloblastoma Cancer Stem Cells Identify Novel Molecular Mediators and Predict Human Medulloblastoma Molecular Classification. Cancer Discov. 2012, 2, 554–568. [Google Scholar] [CrossRef] [Green Version]
- Bahmad, H.F.; Poppiti, R.J. Medulloblastoma cancer stem cells: Molecular signatures and therapeutic targets. J. Clin. Pathol. 2020, 73, 243–249. [Google Scholar] [CrossRef]
- Maude, S.L.; Frey, N.; Shaw, P.A.; Aplenc, R.; Barrett, D.M.; Bunin, N.J.; Chew, A.; Gonzalez, V.E.; Zheng, Z.; Lacey, S.F.; et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. New Engl. J. Med. 2014, 371, 1507–1517. [Google Scholar] [CrossRef] [Green Version]
- Tasian, S.K.; Gardner, R.A. CD19-redirected chimeric antigen receptor-modified T cells: A promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Ther. Adv. Hematol. 2015, 6, 228–241. [Google Scholar] [CrossRef] [PubMed]
- Bielamowicz, K.; Fousek, K.; Byrd, T.T.; Samaha, H.; Mukherjee, M.; Aware, N.; Wu, M.-F.; Orange, J.S.; Sumazin, P.; Man, T.-K.; et al. Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma. J. Neurooncol. 2017, 20, 506–518. [Google Scholar] [CrossRef]
- Lee, D.W.; Kochenderfer, J.N.; Stetler-Stevenson, M.; Cui, Y.K.; Delbrook, C.; Feldman, S.A.; Fry, T.J.; Orentas, R.; Sabatino, M.; Shah, N.N.; et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial. Lancet 2014, 385, 517–528. [Google Scholar] [CrossRef]
- Maude, S.L.; Laetsch, T.W.; Buechner, J.; Rives, S.; Boyer, M.; Bittencourt, H.; Bader, P.; Verneris, M.R.; Stefanski, H.E.; Myers, G.D.; et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N. Engl. J. Med. 2018, 378, 439–448. [Google Scholar] [CrossRef]
- Wrona, E.; Borowiec, M.; Potemski, P. CAR-NK Cells in the Treatment of Solid Tumors. Int. J. Mol. Sci. 2021, 22, 5899. [Google Scholar] [CrossRef]
- Burger, M.C.; Zhang, C.; Harter, P.N.; Romanski, A.; Strassheimer, F.; Senft, C.; Tonn, T.; Steinbach, J.P.; Wels, W.S. CAR-Engineered NK Cells for the Treatment of Glioblastoma: Turning Innate Effectors into Precision Tools for Cancer Immunotherapy. Front. Immunol. 2019, 10, 2683. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Y.; Pardridge, W.M. Mediated efflux of IgG molecules from brain to blood across the blood–brain barrier. J. Neuroimmunol. 2001, 114, 168–172. [Google Scholar] [CrossRef]
- Petersen, C.T.; Krenciute, G. Next Generation CAR T Cells for the Immunotherapy of High-Grade Glioma. Front. Oncol. 2019, 9, 69. [Google Scholar] [CrossRef] [Green Version]
- Razpotnik, R.; Novak, N.; Šerbec, V.; Rajcevic, U. Targeting Malignant Brain Tumors with Antibodies. Front. Immunol. 2017, 8, 1181. [Google Scholar] [CrossRef] [Green Version]
- Pardridge, W.M. Delivery of Biologics Across the Blood–Brain Barrier with Molecular Trojan Horse Technology. BioDrugs 2017, 31, 503–519. [Google Scholar] [CrossRef]
- Jain, R.K.; Di Tomaso, E.; Duda, D.G.; Loeffler, J.S.; Sorensen, A.G.; Batchelor, T.T. Angiogenesis in brain tumours. Nat. Rev. Neurosci. 2007, 8, 610–622. [Google Scholar] [CrossRef] [PubMed]
- Cesca, M.; Bizzaro, F.; Zucchetti, M.; Giavazzi, R. Tumor Delivery of Chemotherapy Combined with Inhibitors of Angiogenesis and Vascular Targeting Agents. Front. Oncol. 2013, 3, 259. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Phoenix, T.N.; Patmore, D.M.; Boop, S.; Boulos, N.; Jacus, M.O.; Patel, Y.T.; Roussel, M.F.; Finkelstein, D.; Goumnerova, L.; Perreault, S.; et al. Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype. Cancer Cell 2016, 29, 508–522. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taube, J.M.; Anders, R.A.; Young, G.D.; Xu, H.; Sharma, R.; McMiller, T.L.; Chen, S.; Klein, A.P.; Pardoll, D.M.; Topalian, S.L.; et al. Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune Escape. Sci. Transl. Med. 2012, 4, 127ra37. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garancher, A.; Suzuki, H.; Haricharan, S.; Chau, L.Q.; Masihi, M.B.; Rusert, J.M.; Norris, P.S.; Carrette, F.; Romero, M.M.; Morrissy, S.A.; et al. Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma. Nat. Neurosci. 2020, 23, 842–853. [Google Scholar] [CrossRef]
- Antonia, S.J.; Villegas, A.; Daniel, D.; Vicente, D.; Murakami, S.; Hui, R.; Yokoi, T.; Chiappori, A.; Lee, K.H.; De Wit, M.; et al. Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2017, 377, 1919–1929. [Google Scholar] [CrossRef] [Green Version]
- Shaverdian, N.; Lisberg, A.E.; Bornazyan, K.; Veruttipong, D.; Goldman, J.W.; Formenti, S.C.; Garon, E.B.; Lee, P. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: A secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol. 2017, 18, 895–903. [Google Scholar] [CrossRef]
- Qian, J.M.; Yu, J.; Kluger, H.M.; Chiang, V.L.S. Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery. Cancer 2016, 122, 3051–3058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Postow, M.A.; Callahan, M.K.; Barker, C.; Yamada, Y.; Yuan, J.; Kitano, S.; Mu, Z.; Rasalan, T.; Adamow, M.; Ritter, E.; et al. Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma. N. Engl. J. Med. 2012, 366, 925–931. [Google Scholar] [CrossRef] [Green Version]
- Wargo, J.A.; Reuben, A.; Cooper, Z.; Oh, K.S.; Sullivan, R.J. Immune Effects of Chemotherapy, Radiation, and Targeted Therapy and Opportunities for Combination with Immunotherapy. Semin. Oncol. 2015, 42, 601–616. [Google Scholar] [CrossRef] [Green Version]
- Cottu, P.; D’Hondt, V.; Dureau, S.; Lerebours, F.; Desmoulins, I.; Heudel, P.-E.; Duhoux, F.; Levy, C.; Mouret-Reynier, M.-A.; Dalenc, F.; et al. Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment of minal breast cancer. Results of the UNICANCER-eoPAL study. Ann. Oncol. 2017, 28, v605. [Google Scholar] [CrossRef]
Trial ID | Title | Phase | Treatment | Target | Indications | Age | N | Status |
---|---|---|---|---|---|---|---|---|
NCT 04730349 | A Study of Bempegaldesleukin (BEMPEG: NKTR-214) in Combination with Nivolumab in Children, Adolescents and Young Adults with Recurrent or Treatment-resistant Cancer (PIVOT IO 020) | 1/2 | i.v. nivolumab with bempegaldesleukin (BEMPEG: NKTR-214) | PD1, CD122 | Ependymoma Ewing sarcoma High-grade glioma Leukemia and lymphoma Medulloblastoma Miscellaneous brain tumors Miscellaneous solid tumors Neuroblastoma Relapsed, refractory malignant neoplasms Rhabdomyosarcoma | <18 and 18–30 years | 228 | Not yet recruiting |
NCT 03130959 | An Investigational Immuno-therapy Study of Nivolumab Monotherapy and Nivolumab in Combination with Ipilimumab in Pediatric Patients with High Grade Primary CNS Malignancies (CheckMate 908) | 2 | Nivolumab, ipilimumab | PD1, CTLA-4 | Various Advanced Cancer (including MB) | 6 months–21 years | 166 | Active, not recruiting |
NCT 03173950 | Immune Checkpoint Inhibitor Nivolumab in People with Recurrent Select Rare CNS Cancers | 2 | i.v. nivolumab | PD1 | Medulloblastoma Ependymoma Pineal region tumors Choroid plexus tumors Atypical/malignant meningioma | >18 years | 180 | Recruiting |
NCT 02359565 | Pembrolizumab in Treating Younger Patients with Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma | 1 | i.v. pembrolizumab | PD1 | Constitutional Mismatch repair Deficiency syndrome Lynch syndrome Malignant glioma Recurrent brain neoplasm Recurrent childhood ependymoma Recurrent diffuse intrinsic pontine glioma Recurrent medulloblastoma Refractory brain neoplasm Refractory diffuse intrinsic pontine glioma Refractory ependymoma Refractory medulloblastoma | 1–29 years | 110 | Recruiting |
NCT 03838042 | INFORM2 Study Uses Nivolumab and Entinostat in Children and Adolescents with High-risk Refractory Malignancies (INFORM2 NivEnt) | 1/2 | Nivolumab and entinostat | PD1 | CNS Tumor Solid Tumor | 6–21 Years | 128 | Recruiting |
NCT 02502708 | Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients with Progressive Primary Malignant Brain Tumors | 1 | Oral indoximod with radiation therapy, temozolomide, or cyclophosphamide and etoposide | IDO | Glioblastoma multiforme Glioma Gliosarcoma Malignant brain tumor Ependymoma Medulloblastoma Diffuse intrinsic pontine glioma Primary CNS tumor | 3–21 years | 81 | Completed |
NCT 04049669 | Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG | 2 | Oral indoximod with combinations of temozolomide, cyclophosphamide, etoposide, lomustine and radiation therapy. | IDO | Glioblastoma Medulloblastoma Ependymoma Diffuse intrinsic pontine glioma | 3–21 years | 140 | Recruiting |
NCT 03389802 | Phase I Study of APX005M in Pediatric CNS Tumors | 1 | i.v. APX005M | CD40 | Glioblastoma Multiforme High-grade astrocytoma, NOS CNS primary tumor, NOS Ependymoma, NOS Diffuse intrinsic pontine gliomas Medulloblastoma | 1–21 years | 45 | Recruiting |
NCT 04167618 | 177Lu-DTPA-Omburtamab Radio-immunotherapy for Recurrent or Refractory Medulloblastoma | 1/2 | 177Lu-DTPA-omburtamab radio-immunotherapy | B7-H3 | Pediatric medulloblastoma | 3–19 years | 40 | Not yet recruiting |
NCT 04743661 | 131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma | 2 | cRIT 131I-omburtamab radio-immunotherapy with Irinotecan, temozolomide, and bevacizumab. | B7-H3 | Recurrent medulloblastoma Recurrent ependymoma | <22 years | 62 | Not yet recruiting |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Voskamp, M.J.; Li, S.; van Daalen, K.R.; Crnko, S.; ten Broeke, T.; Bovenschen, N. Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives. Cancers 2021, 13, 5387. https://doi.org/10.3390/cancers13215387
Voskamp MJ, Li S, van Daalen KR, Crnko S, ten Broeke T, Bovenschen N. Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives. Cancers. 2021; 13(21):5387. https://doi.org/10.3390/cancers13215387
Chicago/Turabian StyleVoskamp, Marije J., Shuang Li, Kim R. van Daalen, Sandra Crnko, Toine ten Broeke, and Niels Bovenschen. 2021. "Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives" Cancers 13, no. 21: 5387. https://doi.org/10.3390/cancers13215387