Trends and developments in translational immunotherapy of brain tumors

doi:10.3969/j.issn.1672-6731.2020.02.003

Abstract

Abstract:

Brain tumors present poor prognosis and high resistance to treatment, bringing devastating burden to patients and the health system. The current standard of care includes surgery with assistant chemoradiotherapy. Due to the independence of the central nervous system as well as the uniqueness of tumor microenvironment (TME), it still warrants further studies in immunotherapy of brain tumors, despite its broad use in other tumors. This article reviewed the recently published and translated Translational Immunotherapy of Brain Tumors and listed the near fundamental results in this field generally. While learning from the experiences from these researches, we also analyzed the current trends in brain immunotherapy, promoting successive explorations in immunotherapy of brain tumors.

Key words: Brian neoplasms, Tumor microenvironment, Immunotherapy, Translational medical research, Review

摘要：

脑肿瘤预后差且治疗困难，为患者和医疗系统带来巨大负担。目前的标准治疗方案是最大范围手术切除辅助放化疗，尽管免疫治疗已广泛应用于肿瘤的治疗，但是由于中枢神经系统的独立性和肿瘤微环境的特殊性，脑肿瘤免疫治疗仍是亟待研究的重要课题。通过对近期出版并翻译的《脑肿瘤免疫治疗及转化研究》进行概述，全面展示近年该领域的重要成果，在吸取研究经验的同时总结发展趋势，为进一步探索脑肿瘤的免疫治疗提供支持。

关键词: 脑肿瘤, 肿瘤微环境, 免疫疗法, 转化医学研究, 综述

LIU Peng-hao, WANG Yu, MA Wen-bin. Trends and developments in translational immunotherapy of brain tumors[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(2): 79-85.

刘芃昊, 王裕, 马文斌. 脑肿瘤免疫治疗及转化研究进展[J]. 中国现代神经疾病杂志, 2020, 20(2): 79-85.

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https://journal11.magtechjournal.com/cjcnn/EN/Y2020/V20/I2/79

References

[1] Sampson JH. Translational immunotherapy of brain tumors[M]. Salt Lake City:Academic Press, 2017.
[2] Sampson JH. Translational immunotherapy of brain tumors[M]. Ma WB, Yang XJ. Trans. Beijing:People's Medical Publishing House, 2019. [Sampson JH.脑肿瘤免疫治疗及转化研究[M].马文斌,杨学军,译.北京:人民卫生出版社, 2019.]
[3] Wainwright DA, Chang AL, Dey M, Balyasnikova IV, Kim CK, Tobias A, Cheng Y, Kim JW, Qiao J, Zhang L, Han Y, Lesniak MS. Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors[J]. Clin Cancer Res, 2014, 20:5290-5301.
[4] Sampson JH, Schmittling RJ, Archer GE, Congdon KL, Nair SK, Reap EA, Desjardins A, Friedman AH, Friedman HS, Herndon JE 2nd, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Mitchell DA. A pilot study of IL-2R α blockade during lymphopenia depletes regulatory T-cells andcorrelates with enhanced immunity in patients with glioblastoma[J]. PLoS One, 2012, 7:E31046.
[5] DiDomenico J, Lamano JB, Oyon D, Li Y, Veliceasa D, Kaur G, Ampie L, Choy W, Lamano JB, Bloch O. The immune checkpoint protein PD-L1 induces and maintains regulatory T cells in glioblastoma[J]. Oncoimmunology, 2018, 7:E1448329.
[6] Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase[J]. J Clin Invest, 2007, 117:2570-2582.
[7] Nakamura T, Shima T, Saeki A, Hidaka T, Nakashima A, Takikawa O, Saito S. Expression of indoleamine 2, 3-dioxygenase and the recruitment of Foxp3-expressing regulatory T cells in the development and progression of uterine cervical cancer[J]. Cancer Sci, 2007, 98:874-881.
[8] Li M, Bolduc AR, Hoda MN, Gamble DN, Dolisca SB, Bolduc AK, Hoang K, Ashley C, McCall D, Rojiani AM, Maria BL, Rixe O, MacDonald TJ, Heeger PS, Mellor AL, Munn DH, Johnson TS. The indoleamine 2, 3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma[J]. J Immunother Cancer, 2014, 2:21.
[9] Long GV, Dummer R, Hamid O, Gajewski TF, Caglevic C, Dalle S, Arance A, Carlino MS, Grob JJ, Kim TM, Demidov L, Robert C, Larkin J, Anderson JR, Maleski J, Jones M, Diede SJ, Mitchell TC. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252):a phase 3, randomised, double-blind study[J]. Lancet Oncol, 2019, 20:1083-1097.
[10] Leone RD, Zhao L, Englert JM, Sun IM, Oh MH, Sun IH, Arwood ML, Bettencourt IA, Patel CH, Wen J, Tam A, Blosser RL, Prchalova E, Alt J, Rais R, Slusher BS, Powell JD. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion[J]. Science, 2019, 366:1013-1021.
[11] Won WJ, Deshane JS, Leavenworth JW, Oliva CR, Griguer CE. Metabolic and functional reprogramming of myeloid-derived suppressor cells and their therapeutic control in glioblastoma[J]. Cell Stress, 2019, 3:47-65.
[12] Lee-Chang C, Rashidi A, Miska J, Lee-Chang C, Rashidi A, Miska J, Zhang P, Pituch KC, Hou D, Xiao T, Fischietti M, Kang SJ, Appin CL, Horbinski C, Platanias LC, Lopez-Rosas A, Han Y, Balyasnikova IV, Lesniak MS. Myeloid-derived suppressive cells promote B cell-mediated immunosuppression via transfer of PD-L1 in glioblastoma[J]. Cancer Immunol Res, 2019, 7:1928-1943.
[13] Li YD, Lamano JB, Lamano JB, Quaggin-Smith J, Veliceasa D, Kaur G, Biyashev D, Unruh D, Bloch O. Tumor-induced peripheral immunosuppression promotes brain metastasis in patients with non-small cell lung cancer[J]. Cancer Immunol Immunother, 2019, 68:1501-1513.
[14] PeereboomDM, Alban TJ, Grabowski MM, Alvarado AG, Otvos B, Bayik D, Roversi G, McGraw M, Huang P, Mohammadi AM, Kornblum HI, Radivoyevitch T, Ahluwalia MS, Vogelbaum MA, Lathia JD. Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells[J]. JCI Insight, 2019, 4:130748.
[15] Otvos B, Silver DJ, Mulkearns-Hubert EE, Alvarado AG, Turaga SM, Sorensen MD, Rayman P, Flavahan WA, Hale JS, Stoltz K, Sinyuk M, Wu Q, Jarrar A, Kim SH, Fox PL, Nakano I, Rich JN, Ransohoff RM, Finke J, Kristensen BW, Vogelbaum MA, Lathia JD. Cancer stem cell-secreted macrophage migration inhibitory factor stimulates myeloid derived suppressor cell function and facilitates glioblastoma immune evasion[J]. Stem Cells, 2016, 34:2026-2039.
[16] Nandu H, Wen PY, Huang RY. Imaging in neuro-oncology[J]. Ther Adv Neurol Disord, 2018, 11:ID1756286418759865.
[17] Tofts PS. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging[J]. J Mag Reson Imaging, 1997, 7:91-101.
[18] Sundgren PC, Fan X, Weybright P, Welsh RC, Carlos RC, Petrou M, McKeever PE, Chenevert TL. Differentiation of recurrent brain tumor versus radiation injury using diffusion tensor imaging in patients with new contrast-enhancing lesions[J]. Magn Reson Imaging, 2006, 24:1131-1142.
[19] Kincaid PK, El-Saden SM, Park SH, Goy BW. Cerebral gangliogliomas:preoperative grading using FDG-PET and 201Tl-SPECT[J]. AJNR Am J Neuroradiol, 1998, 19:801-806.
[20] Kong Z, Jiang C, Zhu R, Feng S, Wang Y, Li J, Chen W, Liu P, Zhao D, Ma W, Wang Y, Cheng X. 18F-FDG-PET-based radiomics features to distinguish primary central nervous system lymphoma from glioblastoma[J]. Neuro Image Clin, 2019, 23:101912.
[21] Filley AC, Henriquez M, Dey M. Recurrent glioma clinical trial, CheckMate-143:the game is not over yet[J]. Oncotarget, 2017, 8:91779-91794.
[22] Sampson JH, Gunn MD, Fecci PE, Ashley DM. Brain immunology and immunotherapy in brain tumours[J]. Nat Rev Cancer, 2020, 20:12-25.
[23] Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, Wang AC, Ellingson BM, Rytlewski JA, Sanders CM, Kawaguchi ES, Du L, Li G, Yong WH, Gaffey SC, Cohen AL, Mellinghoff IK, Lee EQ, Reardon DA, O'Brien BJ, Butowski NA, Nghiemphu PL, Clarke JL, Arrillaga-Romany IC, Colman H, Kaley TJ, de Groot JF, Liau LM, Wen PY, Prins RM. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma[J]. Nat Med, 2019, 25:477-486.
[24] Schumacher T, Bunse L, Pusch S, Sahm F, Wiestler B, Quandt J, Menn O, Osswald M, Oezen I, Ott M, Keil M, Balß J, Rauschenbach K, Grabowska AK, Vogler I, Diekmann J, Trautwein N, Eichmüller SB, Okun J, Stevanovi S, Riemer AB, Sahin U, Friese MA, Beckhove P, von Deimling A, Wick W, Platten M. A vaccine targeting mutant IDH1 induces antitumour immunity[J]. Nature, 2014, 512:324-327.
[25] Pellegatta S, Valletta L, Corbetta C, Patanè M, Zucca I, Riccardi Sirtori F, Bruzzone MG, Fogliatto G, Isacchi A, Pollo B, Finocchiaro G. Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma[J]. Acta Neuropathol Commun, 2015, 3:4.
[26] Sampson JH, Aldape KD, Archer GE, Coan A, Desjardins A, Friedman AH, Friedman HS, Gilbert MR, Herndon JE, McLendon RE, Mitchell DA, Reardon DA, Sawaya R, Schmittling R, Shi W, Vredenburgh JJ, Bigner DD, Heimberger AB. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvⅢ-expressing tumor cells in patients with glioblastoma[J]. Neuro Oncol, 2011, 13:324-333.
[27] Schuster J, Lai RK, Recht LD, Reardon DA, Paleologos NA, Groves MD, Mrugala MM, Jensen R, Baehring JM, Sloan A, Archer GE, Bigner DD, Cruickshank S, Green JA, Keler T, Davis TA, Heimberger AB, Sampson JH. A phase Ⅱ, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma:the ACT Ⅲ study[J]. Neuro Oncol, 2015, 17:854-861.
[28] Babu R, Adamson DC. Rindopepimut:an evidence-based review of its therapeutic potential in the treatment of EGFRvⅢ-positive glioblastoma[J]. Core Evid, 2012, 7:93-103.
[29] Paff M, Alexandru-Abrams D, Hsu FP, Bota DA. The evolution of the EGFRv Ⅲ(rindopepimut) immunotherapy for glioblastoma multiforme patients[J]. Hum Vaccin Immunother, 2014, 10:3322-3331.
[30] Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, Ashby L, Mechtler L, Goldlust SA, Iwamoto F, Drappatz J, O'Rourke DM, Wong M, Hamilton MG, Finocchiaro G, Perry J, Wick W, Green J, He Y, Turner CD, Yellin MJ, Keler T, Davis TA, Stupp R, Sampson JH; ACT Ⅳ Trial Investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRv Ⅲ-expressing glioblastoma (ACT Ⅳ):a randomised, double-blind, international phase 3 trial[J]. Lancet Oncol, 2017, 18:1373-1385.
[31] Liau LM, Ashkan K, Tran DD, Campian JL, Trusheim JE, Cobbs CS, Heth JA, Salacz M, Taylor S, D'Andre SD, Iwamoto FM, Dropcho EJ, Moshel YA, Walter KA, Pillainayagam CP, Aiken R, Chaudhary R, Goldlust SA, Bota DA, Duic P, Grewal J, Elinzano H, Toms SA, Lillehei KO, Mikkelsen T, Walbert T, Abram SR, Brenner AJ, Brem S, Ewend MG, Khagi S, Portnow J, Kim LJ, Loudon WG, Thompson RC, Avigan DE, Fink KL, Geoffroy FJ, Lindhorst S, Lutzky J, Sloan AE, Schackert G, Krex D, Meisel HJ, Wu J, Davis RP, Duma C, Etame AB, Mathieu D, Kesari S, Piccioni D, Westphal M, Baskin DS, New PZ, Lacroix M, May SA, Pluard TJ, Tse V, Green RM, Villano JL, Pearlman M, Petrecca K, Schulder M, Taylor LP, Maida AE, Prins RM, Cloughesy TF, Mulholland P, Bosch ML. First results on survival from a large phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma[J]. J Transl Med, 2018, 16:142.
[32] Phuphanich S, Wheeler CJ, Rudnick JD, Mazer M, Wang H, Nuño MA, Richardson JE, Fan X, Ji J, Chu RM, Bender JG, Hawkins ES, Patil CG, Black KL, Yu JS. Phase Ⅰ trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma[J]. Cancer Immunol Immunother, 2013, 62:125-135.
[33] Wen PY, Reardon DA, Armstrong TS, Phuphanich S, Aiken RD, Landolfi JC, Curry WT, Zhu JJ, Glantz M, Peereboom DM, Markert JM, LaRocca R, O'Rourke DM, Fink K, Kim L, Gruber M, Lesser GJ, Pan E, Kesari S, Muzikansky A, Pinilla C, Santos RG, Yu JS. A randomized double-blind placebo-controlled phase Ⅱ trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma[J]. Clin Cancer Res, 2019, 25:5799-5807.
[34] Akhavan D, Alizadeh D, Wang D, Weist MR, Shepphird JK, Brown CE. CAR T cells for brain tumors:lessons learned and road ahead[J]. Immunol Rev, 2019, 290:60-84.
[35] O'Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJ, Martinez-Lage M, Brem S, Maloney E, Shen A, Isaacs R, Mohan S, Plesa G, Lacey SF, Navenot JM, Zheng Z, Levine BL, Okada H, June CH, Brogdon JL, Maus MV. A single dose of peripherally infused EGFRv Ⅲ-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma[J]. Sci Transl Med, 2017, 9:EAAA0984.
[36] Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, Ostberg JR, Blanchard MS, Kilpatrick J, Simpson J, Kurien A, Priceman SJ, Wang X, Harshbarger TL, D'Apuzzo M, Ressler JA, Jensen MC, Barish ME, Chen M, Portnow J, Forman SJ, Badie B. Regression of glioblastoma after chimeric antigen receptor T-cell therapy[J]. N Engl J Med, 2016, 375:2561-2569.
[37] Goff SL, Morgan RA, Yang JC, Sherry RM, Robbins PF, Restifo NP, Feldman SA, Lu YC, Lu L, Zheng Z, Xi L, Epstein M, Mclntyre LS, Malekzadeh P, Raffeld M, Fine HA, Rosenberg SA. Pilot trial of adoptive transfer of chimeric antigen receptor-transduced T cells targeting EGFRv Ⅲ in patients with glioblastoma[J]. J Immunother, 2019, 42:126-135.
[38] Morgan RA, Johnson LA, Davis JL, Zheng Z, Woolard KD, Reap EA, Feldman SA, Chinnasamy N, Kuan CT, Song H, Zhang W, Fine HA, Rosenberg SA. Recognition of glioma stem cells by genetically modified T cells targeting EGFRv Ⅲ and development of adoptive cell therapy for glioma[J]. Hum Gene Ther, 2012, 23:1043-1053.
[39] van den Bent MJ, Gao Y, Kerkhof M, Kros JM, Gorlia T, van Zwieten K, Prince J, van Duinen S, Sillevis Smitt PA, Taphoorn M, French PJ. Changes in the EGFR amplification and EGFRv Ⅲ expression between paired primary and recurrent glioblastomas[J]. Neuro Oncol, 2015, 17:935-941.
[40] Martikainen M, Essand M. Virus-based immunotherapy of glioblastoma[J]. Cancers (Basel), 2019, 11:E186.
[41] Harrington K, Freeman DJ, Kelly B, Harper J, Soria JC. Optimizing oncolytic virotherapy in cancer treatment[J]. Nat Rev Drug Discov, 2019, 18:689-706.
[42] Markert JM, Liechty PG, Wang W, Gaston S, Braz E, Karrasch M, Nabors LB, Markiewicz M, Lakeman AD, Palmer CA, Parker JN, Whitley RJ, Gillespie GY. Phase Ⅰ b trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM[J]. Mol Ther, 2009, 17:199-207.
[43] Lang FF, Conrad C, Gomez-Manzano C, Yung WK, Sawaya R, Weinberg JS, Prabhu SS, Rao G, Fuller GN, Aldape KD, Gumin J, Vence LM, Wistuba I, Rodriguez-Canales J, Villalobos PA, Dirven CM, Tejada S, Valle RD, Alonso MM, Ewald B, Peterkin JJ, Tufaro F, Fueyo J. Phase Ⅰ study of DNX-2401(Delta-24-RGD) oncolytic adenovirus:replication and immunotherapeutic effects in recurrent malignant glioma[J]. J Clin Oncol, 2018, 36:1419-1427.
[44] Jiang H, Gomez-Manzano C, Rivera-Molina Y, Lang FF, Conrad CA, Fueyo J. Oncolytic adenovirus research evolution:from cell-cycle checkpoints to immune checkpoints[J]. Curr Opin Virol, 2015, 13:33-39.
[45] Jiang H, Clise-Dwyer K, Ruisaard KE, Fan X, Tian W, Gumin J, Lamfers ML, Kleijn A, Lang FF, Yung WK, Vence LM, Gomez-Manzano C, Fueyo J. Delta-24-RGD oncolytic adenovirus elicits anti-glioma immunity in an immunocompetent mouse model[J]. PLoS One, 2014, 9:E97407.
[46] Saha D, Martuza RL, Rabkin SD. Macrophage polarization contributes to glioblastoma eradication by combination immunovirotherapy and immune checkpoint blockade[J]. Cancer Cell, 2017, 32:253-267.
[47] Saha D, Martuza RL, Rabkin SD. Oncolytic herpes simplex virus immunovirotherapy in combination with immune checkpoint blockade to treat glioblastoma[J]. Immunotherapy, 2018, 10:779-786.
[48] Mitchell LA, Lopez Espinoza F, Mendoza D, Kato Y, Inagaki A, Hiraoka K, Kasahara N, Gruber HE, Jolly DJ, Robbins JM. Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable antitumor immunity in a mouse glioma model[J]. Neuro Oncol, 2017, 19:930-939.
[49] Speranza MC, Passaro C, Ricklefs F, Kasai K, Klein SR, Nakashima H, Kaufmann JK, Ahmed AK, Nowicki MO, Obi P, Bronisz A, Aguilar-Cordova E, Aguilar LK, Guzik BW, Breakefield X, Weissleder R, Freeman GJ, Reardon DA, Wen PY, Chiocca EA, Lawler SE. Preclinical investigation of combined gene-mediated cytotoxic immunotherapy and immune checkpoint blockade in glioblastoma[J]. Neuro Oncol, 2018, 20:225-235.
[50] Woroniecka K, Chongsathidkiet P, Rhodin KE. T-cell exhaustion signatures vary with tumor type and are severe in glioblastoma[J]. Clin Cancer Res, 2018, 24:4175-4186.
[51] Kim JE, Patel MA, Mangraviti A, Kim ES, Theodros D, Velarde E, Liu A, Sankey EW, Tam A, Xu H, Mathios D, Jackson CM, Harris-Bookman S, Garzon-Muvdi T, Sheu M, Martin AM, Tyler BM, Tran PT, Ye X, Olivi A, Taube JM, Burger PC, Drake CG, Brem H, Pardoll DM, Lim M. Combination therapy with anti-PD-1, anti-TIM-3, and focal radiation results in regression of murine gliomas[J]. Clin Cancer Res, 2017, 23:124-136.
[52] 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[J]. DNA Cell Biol, 2014, 33:245-250.

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