脑胶质瘤免疫检查点抑制剂及其临床研究进展

doi:10.3969/j.issn.1672-6731.2020.02.005

摘要/Abstract

摘要：

脑胶质瘤是临床最常见的原发性颅内恶性肿瘤，尤以胶质母细胞瘤预后最差。近年来，靶向免疫检查点的免疫治疗在多种实体肿瘤中展现出良好疗效，成为胶质瘤药物治疗领域的潜在突破口，受到国内外神经外科和神经肿瘤科医师的关注。通过综述免疫检查点分子及抑制剂临床研究进展，介绍免疫治疗在胶质瘤领域的研究现状，以期对我国胶质瘤免疫治疗后续临床研究设计和开展提供参考。

关键词: 神经胶质瘤, 免疫抑制剂, 免疫疗法, 综述

Abstract:

Glioma is the most common primary intracranial malignant tumor, and glioblastoma has the worst prognosis. In recent years, immunotherapy targeting immune checkpoints has shown promising results in various solid tumors, and has also become a potential breakthrough in the field of glioma treatment, which has attracted the attention of worldwide neurosurgeons and neuro-oncologists. This paper reviews the literature about immune checkpoint molecules and the clinical trials of immune checkpoint inhibitors, and briefly introduces the research status of immunotherapy in glioma. We hope to provide some references for the design and development of subsequent clinical studies of glioma immunotherapy in China.

Key words: Glioma, Immunosuppressive agents, Immunotherapy, Review

丁骁杰, 陈弟, 唐超, 姚瑜. 脑胶质瘤免疫检查点抑制剂及其临床研究进展[J]. 中国现代神经疾病杂志, 2020, 20(2): 96-104.

DING Xiao-jie, CHEN Di, TANG Chao, YAO Yu. Advance of immune checkpoint inhibitors and clinical trials in glioma[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(2): 96-104.

http://journal11.magtechjournal.com/cjcnn/CN/Y2020/V20/I2/96

参考文献

[1] Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report:primary brain and central nervous system tumors diagnosed in The United States in 2006-2010[J]. Neuro Oncol, 2013, 15 Suppl 2:ii1-56.
[2] Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, Wrensch MR, Barnholtz-Sloan JS. The epidemiology of glioma in adults:a "state of the science" review[J]. Neuro Oncol, 2014, 16:896-913.
[3] Ostrom QT, Gittleman H, Stetson L, Virk SM, Barnholtz-Sloan JS. Epidemiology of gliomas[J]. Cancer Treat Res, 2015, 163:1-14.
[4] Shen F, Wu CX, Yao Y, Peng P, Qin ZY, Wang Y, Zheng Y, Zhou LF. Transition over 35 years in the incidence rates of primary central nervous system tumors in Shanghai, China and histological subtyping based on a single center experience spanning 60 years[J]. Asian Pac J Cancer Prev, 2013, 14:7385-7393.
[5] Bersanelli M, Buti S. From targeting the tumor to targeting the immune system:transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis[J]. World J Clin Oncol, 2017, 8:37-53.
[6] Romani M, Pistillo MP, Carosio R, Morabito A, Banelli B. Immune checkpoints and innovative therapies in glioblastoma[J]. Front Oncol, 2018, 8:464.
[7] Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death[J]. EMBO J, 1992, 11:3887-3895.
[8] Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation[J]. J Exp Med, 2000, 192:1027-1034.
[9] Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ. PD-L2 is a second ligand for PD-1 and inhibits T cell activation[J]. Nat Immunol, 2001, 2:261-268.
[10] Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC, Mischel PS, Stokoe D, Pieper RO. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma[J]. Nat Med, 2007, 13:84-88.
[11] Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy[J]. Nat Rev Cancer, 2012, 12:252-264.
[12] Azuma T, Yao S, Zhu G, Flies AS, Flies SJ, Chen L. B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells[J]. Blood, 2008, 111:3635-3643.
[13] Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+T cells[J]. Cancer Res, 2004, 64:1140-1145.
[14] Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, Rietz C, Flies DB, Lau JS, Zhu G, Tamada K, Chen L. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity[J]. Cancer Res, 2005, 65:1089-1096.
[15] Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade[J]. Proc Natl Acad Sci USA, 2002, 99:12293-12297.
[16] Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, Rosenberg SA. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired[J]. Blood, 2009, 114:1537-1544.
[17] Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, Wunderlich JR, Mixon A, Farid S, Dudley ME, Hanada K, Almeida JR, Darko S, Douek DC, Yang JC, Rosenberg SA. PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors[J]. J Clin Invest, 2014, 124:2246-2259.
[18] Haanen JB, Robert C. Immune checkpoint inhibitors[J]. Prog Tumor Res, 2015, 42:55-66.
[19] Heiland DH, Haaker G, Delev D, Mercas B, Masalha W, Heynckes S, Gäbelein A, Pfeifer D, Carro MS, Weyerbrock A, Prinz M, Schnell O. Comprehensive analysis of PD-L1 expression in glioblastoma multiforme[J]. Oncotarget, 2017, 8:42214-42225.
[20] Nduom EK, Wei J, Yaghi NK, Huang N, Kong LY, Gabrusiewicz K, Ling X, Zhou S, Ivan C, Chen JQ, Burks JK, Fuller GN, Calin GA, Conrad CA, Creasy C, Ritthipichai K, Radvanyi L, Heimberger AB. PD-L1 expression and prognostic impact in glioblastoma[J]. Neuro Oncol, 2016, 18:195-205.
[21] Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, Sengupta S, Frank I, Parker AS, Zincke H, Blute ML, Sebo TJ, Cheville JC, Kwon ED. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up[J]. Cancer Res, 2006, 66:3381-3385.
[22] Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, Higuchi T, Yagi H, Takakura K, Minato N, Honjo T, Fujii S. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+T lymphocytes are prognostic factors of human ovarian cancer[J]. Proc Natl Acad Sci USA, 2007, 104:3360-3365.
[23] Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas[J]. Clin Cancer Res, 2014, 20:2773-2782.
[24] Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzan M, Mattei MG, Golstein P. A new member of the immunoglobulin superfamily:CTLA-4[J]. Nature, 1987, 328:267-270.
[25] Lee KM, Chuang E, Griffin M, Khattri R, Hong DK, Zhang W, Straus D, Samelson LE, Thompson CB, Bluestone JA. Molecular basis of T cell inactivation by CTLA-4[J]. Science, 1998, 282:2263-2266.
[26] Fong B, Jin R, Wang X, Safaee M, Lisiero DN, Yang I, Li G, Liau LM, Prins RM. Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients[J]. PLoS One, 2012, 7:E32614.
[27] Linsley PS, Wallace PM, Johnson J, Gibson MG, Greene JL, Ledbetter JA, Singh C, Tepper MA. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule[J]. Science, 1992, 257:792-795.
[28] Lenschow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, Gibson MG, Linsley PS, Bluestone JA. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig[J]. Science, 1992, 257:789-792.
[29] Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors[J]. Proc Natl Acad Sci USA, 2010, 107:4275-4280.
[30] Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus ipilimumab in advanced melanoma[J]. N Engl J Med, 2013, 369:122-133.
[31] Krambeck AE, Thompson RH, Dong H, Lohse CM, Park ES, Kuntz SM, Leibovich BC, Blute ML, Cheville JC, Kwon ED. B7-H4 expression in renal cell carcinoma and tumor vasculature:associations with cancer progression and survival[J]. Proc Natl Acad Sci USA, 2006, 103:10391-10396.
[32] Tringler B, Zhuo S, Pilkington G, Torkko KC, Singh M, Lucia MS, Heinz DE, Papkoff J, Shroyer KR. B7-h4 is highly expressed in ductal and lobular breast cancer[J]. Clin Cancer Res, 2005, 11:1842-1848.
[33] Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, Scardino PT, Sharma P, Allison JP. B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome[J]. Proc Natl Acad Sci USA, 2007, 104:19458-19463.
[34] Yao Y, Wang X, Jin K, Zhu J, Wang Y, Xiong S, Mao Y, Zhou L. B7-H4 is preferentially expressed in non-dividing brain tumor cells and in a subset of brain tumor stem-like cells[J]. J Neurooncol, 2008, 89:121-129.
[35] Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, Chapoval AI, Flies DB, Bajorath J, Chen L. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity[J]. Immunity, 2003, 18:849-861.
[36] Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, Dong H, Sica GL, Zhu G, Tamada K, Chen L. B7-H3:a costimulatory molecule for T cell activation and IFN-gamma production[J]. Nat Immunol, 2001, 2:269-274.
[37] Yao Y, Ye H, Qi Z, Mo L, Yue Q, Baral A, Hoon DS, Vera JC, Heiss JD, Chen CC, Zhang J, Jin K, Wang Y, Zang X, Mao Y, Zhou L. B7-H4(B7x)-mediated cross-talk between glioma-initiating cells and macrophages via the IL6/JAK/STAT3 pathway lead to poor prognosis in glioma patients[J]. Clin Cancer Res, 2016, 22:2778-2790.
[38] Jeon H, Vigdorovich V, Garrett-Thomson SC, Janakiram M, Ramagopal UA, Abadi YM, Lee JS, Scandiuzzi L, Ohaegbulam KC, Chinai JM, Zhao R, Yao Y, Mao Y, Sparano JA, Almo SC, Zang X. Structure and cancer immunotherapy of the B7 family member B7x[J]. Cell Rep, 2014, 9:1089-1098.
[39] Prendergast GC, Smith C, Thomas S, Mandik-Nayak L, Laury-Kleintop L, Metz R, Muller AJ. Indoleamine 2, 3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer[J]. Cancer Immunol Immunother, 2014, 63:721-735.
[40] Godin-Ethier J, Hanafi LA, Piccirillo CA, Lapointe R. Indoleamine 2, 3-dioxygenase expression in human cancers:clinical and immunologic perspectives[J]. Clin Cancer Res, 2011, 17:6985-6991.
[41] Löb S, Königsrainer A, Rammensee HG, Opelz G, Terness P. Inhibitors of indoleamine-2, 3-dioxygenase for cancer therapy:can we see the wood for the trees[J]?Nat Rev Cancer, 2009, 9:445-452.
[42] Mbongue JC, Nicholas DA, Torrez TW, Kim NS, Firek AF, Langridge WH. The role of indoleamine 2, 3-dioxygenase in immune suppression and autoimmunity[J]. Vaccines (Basel), 2015, 3:703-729.
[43] Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2, 3-dioxygenase[J]. J Exp Med, 2002, 196:459-468.
[44] Chung DJ, Rossi M, Romano E, Ghith J, Yuan J, Munn DH, Young JW. Indoleamine 2, 3-dioxygenase-expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells[J]. Blood, 2009, 114:555-563.
[45] Mellor AL, Munn DH. Physiologic control of the functional status of Foxp3+ regulatory T cells[J]. J Immunol, 2011, 186:4535-4540.
[46] Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells[J]. J Immunol, 2010, 185:3190-3198.
[47] Wainwright DA, Balyasnikova IV, Chang AL, Ahmed AU, Moon KS, Auffinger B, Tobias AL, Han Y, Lesniak MS. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival[J]. Clin Cancer Res, 2012, 18:6110-6121.
[48] Zhai L, Lauing KL, Chang AL, Dey M, Qian J, Cheng Y, Lesniak MS, Wainwright DA. The role of IDO in brain tumor immunotherapy[J]. J Neurooncol, 2015, 123:395-403.
[49] O'connor JC, Lawson MA, André C, Briley EM, Szegedi SS, Lestage J, Castanon N, Herkenham M, Dantzer R, Kelley KW. Induction of IDO by bacille Calmette-Guérin is responsible for development of murine depressive-like behavior[J]. J Immunol, 2009, 182:3202-3212.
[50] Uyttenhove C, Pilotte L, Théate I, Stroobant V, Colau D, Parmentier N, Boon T, Van Den Eynde BJ. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2, 3-dioxygenase[J]. Nat Med, 2003, 9:1269-1274.
[51] Hanihara M, Kawataki T, Oh-Oka K, Mitsuka K, Nakao A, Kinouchi H. Synergistic antitumor effect with indoleamine 2, 3-dioxygenase inhibition and temozolomide in a murine glioma model[J]. J Neurosurg, 2016, 124:1594-1601.
[52] Das M, Zhu C, Kuchroo VK. TIM-3 and its role in regulating anti-tumor immunity[J]. Immunol Rev, 2017, 276:97-111.
[53] Dekruyff RH, Bu X, Ballesteros A, Santiago C, Chim YL, Lee HH, Karisola P, Pichavant M, Kaplan GG, Umetsu DT, Freeman GJ, Casasnovas JM. T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells[J]. J Immunol, 2010, 184:1918-1930.
[54] Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colgan JD, Hirashima M, Uede T, Takaoka A, Yagita H, Jinushi M. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1[J]. Nat Immunol, 2012, 13:832-842.
[55] 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.
[56] Li G, Wang Z, Zhang C, Liu X, Cai J, Wang Z, Hu H, Wu F, Bao Z, Liu Y, Zhao L, Liang T, Yang F, Huang R, Zhang W, Jiang T. Molecular and clinical characterization of TIM-3 in glioma through 1, 024 samples[J]. Oncoimmunology, 2017, 6:E1328339.
[57] Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA. Role of LAG-3 in regulatory T cells[J]. Immunity, 2004, 21:503-513.
[58] Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, Betts MR, Freeman GJ, Vignali DA, Wherry EJ. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection[J]. Nat Immunol, 2009, 10:29-37.
[59] Workman CJ, Wang Y, El Kasmi KC, Pardoll DM, Murray PJ, Drake CG, Vignali DA. LAG-3 regulates plasmacytoid dendritic cell homeostasis[J]. J Immunol, 2009, 182:1885-1891.
[60] Zhang Q, Chikina M, Szymczak-Workman AL, Horne W, Kolls JK, Vignali KM, Normolle D, Bettini M, Workman CJ, Vignali DA. LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes[J]. Sci Immunol, 2017, 2:EAAH4569.
[61] Workman CJ, Vignali DA. The CD4-related molecule, LAG-3(CD223), regulates the expansion of activated T cells[J]. Eur J Immunol, 2003, 33:970-979.
[62] Andrews LP, Marciscano AE, Drake CG, Vignali DA. LAG3(CD223) as a cancer immunotherapy target[J]. Immunol Rev, 2017, 276:80-96.
[63] Huang RY, Eppolito C, Lele S, Shrikant P, Matsuzaki J, Odunsi K. LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model[J]. Oncotarget, 2015, 6:27359-27377.
[64] Jing W, Gershan JA, Weber J, Tlomak D, Mcolash L, Sabatos-Peyton C, Johnson BD. Combined immune checkpoint protein blockade and low dose whole body irradiation as immunotherapy for myeloma[J]. J Immunother Cancer, 2015, 3:2.
[65] Kouo T, Huang L, Pucsek AB, Cao M, Solt S, Armstrong T, Jaffee E. Galectin-3 shapes antitumor immune responses by suppressing CD8+ T cells via LAG-3 and inhibiting expansion of plasmacytoid dendritic cells[J]. Cancer Immunol Res, 2015, 3:412-423.
[66] Ascierto PA, Bono P, Bhatia S, Melero I, Nyakas MS, Svane IM, Larkin J, Gomez-Roca C, Schadendorf D, Dummer R, Marabelle A, Hoeller C, Maurer M, Harbison CT, Mitra P, Suryawanshi S, Thudium K, Muñoz Couselo E. Efficacy of BMS-986016, a monoclonal antibody that targets lymphocyte activation gene-3(LAG-3), in combination with nivolumab in pts with melanoma who progressed during prior anti-PD-1/PD-L1 therapy (mel prior IO) in all-comer and biomarker-enriched populations[J]. Annals of Oncology, 2017, 28(Suppl_5):611-612.
[67] Pegram HJ, Andrews DM, Smyth MJ, Darcy PK, Kershaw MH. Activating and inhibitory receptors of natural killer cells[J]. Immunol Cell Biol, 2011, 89:216-224.
[68] Beksac K, Beksac M, Dalva K, Karaagaoglu E, Tirnaksiz MB. Impact of "Killer Immunoglobulin-Like Receptor/Ligand" genotypes on outcome following surgery among patients with colorectal cancer:activating kirs are associated with long-term disease free survival[J]. PLoS One, 2015, 10:E0132526.
[69] Chester C, Fritsch K, Kohrt HE. Natural killer cell immunomodulation:targeting activating, inhibitory, and co-stimulatory receptor signaling for cancer immunotherapy[J]. Front Immunol, 2015, 6:601.
[70] Perrin G, Speiser D, Porret A, Quiquerez AL, Walker PR, Dietrich PY. Sister cytotoxic CD8+ T cell clones differing in natural killer inhibitory receptor expression in human astrocytoma[J]. Immunol Lett, 2002, 81:125-132.
[71] Schalper KA, Rodriguez-Ruiz ME, Diez-Valle R, López-Janeiro A, Porciuncula A, Idoate MA, Inogés S, de Andrea C, López-Diaz de Cerio A, Tejada S, Berraondo P, Villarroel-Espindola F, Choi J, Gúrpide A, Giraldez M, Goicoechea I, Gallego Perez-Larraya J, Sanmamed MF, Perez-Gracia JL, Melero I. Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma[J]. Nat Med, 2019, 25:470-476.
[72] 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.
[73] Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R, Zwirtes R, Strauss L, Paliwal P, Harbison CT, Reardon DA, Sampson JH. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma:results from exploratory phase Ⅰ cohorts of CheckMate 143[J]. Neuro Oncol, 2018, 20:674-686.
[74] Reardon DA, Omuro A, Brandes AA, Rieger J, Wick A, Sepulveda J, Phuphanich S, De Souza P, Ahluwalia MS, Lim M, Vlahovic G, Sampson J. OS10.3 randomized phase 3 study evaluating the efficacy and safety of Nivolumab vs Bevacizumab in patients with recurrent glioblastoma:CheckMate 143[J]. Neuro Oncology, 2017, 19(Suppl 3):iii21.
[75] Kurz SC, Wen PY. Quo vadis-do immunotherapies have a role in glioblastoma[J]?Curr Treat Options Neurol, 2018, 20:14.
[76] Bristol-Myers Squibb Announces Phase 3 CheckMate-498 study did not meet primary endpoint of overall survival with opdivo (nivolumab) plus radiation in patients with newly diagnosed MGMT-unmethylated glioblastoma multiforme. Princeton, NJ:Bristol-Myers Squibb Company, 2019[2019-11-04]. https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-phase-3-checkmate-498-study-did.
[77] Bristol-Myers Squibb Provides Update on Phase 3 Opdivo (Nivolumab) CheckMate-548 trial in patients with newly diagnosed MGMT-methylated glioblastoma multiforme. Princeton, NJ:Bristol-Myers Squibb Company, 2019[2019-11-04]. https://bit.ly/2ktBxYb
[78] Lukas RV, Rodon J, Becker K, Wong ET, Shih K, Touat M, Fassò M, Osborne S, Molinero L, O'Hear C, Grossman W, Baehring J. Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma[J]. J Neurooncol, 2018, 140:317-328.
[79] Grossman SA, Ye X, Lesser G, Sloan A, Carraway H, Desideri S, Piantadosi S; NABTT CNS Consortium. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide[J]. Clin Cancer Res, 2011, 17:5473-5480.
[80] Mathios D, Kim JE, Mangraviti A, Phallen J, Park CK, Jackson CM, Garzon-Muvdi T, Kim E, Theodros D, Polanczyk M, Martin AM, Suk I, Ye X, Tyler B, Bettegowda C, Brem H, Pardoll DM, Lim M. Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM[J]. Sci Transl Med, 2016, 8:370RA180.
[81] Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J, Durham N, Meyer C, Harris TJ, Albesiano E, Pradilla G, Ford E, Wong J, Hammers HJ, Mathios D, Tyler B, Brem H, Tran PT, Pardoll D, Drake CG, Lim M. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas[J]. Int J Radiat Oncol Biol Phys, 2013, 86:343-349.
[82] Shepard MJ, Xu Z, Donahue J, Eluvathingal Muttikkal TJ, Cordeiro D, Hansen L, Mohammed N, Gentzler RD, Larner J, Fadul CE, Sheehan JP. Stereotactic radiosurgery with and without checkpoint inhibition for patients with metastatic non-small cell lung cancer to the brain:a matched cohort study[J]. J Neurosurg, 2019. [Epub ahead of print]
[83] Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, Li XD, Mauceri H, Beckett M, Darga T, Huang X, Gajewski TF, Chen ZJ, Fu YX, Weichselbaum RR. STING-dependent cytosolic DNA sensing promotes radiation-induced type Ⅰ interferon-dependent antitumor immunity in immunogenic tumors[J]. Immunity, 2014, 41:843-852.
[84] Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors:immune-related response criteria[J]. Clin Cancer Res, 2009, 15:7412-7420.

选择文件类型/文献管理软件名称

选择包含的内容

2 脑胶质瘤免疫检查点抑制剂及其临床研究进展

Advance of immune checkpoint inhibitors and clinical trials in glioma

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	薛蓉, 张轩. 睡眠障碍对脑血管病的影响[J]. 中国现代神经疾病杂志, 2023, 23(8): 659-662.
[2]	张鹏, 陈涛, 许莉. 成人失眠认知行为疗法关键技术与流程改进建议[J]. 中国现代神经疾病杂志, 2023, 23(8): 663-667.
[3]	张轩, 薛蓉. 特发性快速眼动睡眠期行为障碍向神经系统变性疾病转化的生物学标志物研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 668-673.
[4]	刘引, 汤永红, 翟锦霞, 邱媛. 慢性低度炎症与睡眠障碍研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 674-677.
[5]	于洁洋, 张亚男, 李惠敏, 黄真灿, 李宛儒, 王赞. 发作性睡病与焦虑研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 678-682.
[6]	库成心, 邓丽影, 谢亮. 缺血性卒中继发日间过度思睡研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 683-686.
[7]	姜佳凤, 赵莲花, 赵伟. 褪黑素在阿尔茨海默病病理损害机制中的作用[J]. 中国现代神经疾病杂志, 2023, 23(8): 687-692.
[8]	黄沛, 王刚. 功能性帕金森综合征诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(8): 738-741.
[9]	洪涛, 唐斌. 如何成为一名优秀的颅底外科医师[J]. 中国现代神经疾病杂志, 2023, 23(7): 571-574.
[10]	张庆硕, 宋丹丹, 周世越, 张金璐, 韩晓旭, 许顺良. 功能性步态障碍诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(7): 604-609.
[11]	潘希娟, 邢英琦, 刘玉梅. 脑小血管病影像学评分方法[J]. 中国现代神经疾病杂志, 2023, 23(7): 633-637.
[12]	俞淑凤, 李宁, 徐健, 王鹏. 颈动脉漂浮血栓相关缺血性卒中诊断与治疗进展[J]. 中国现代神经疾病杂志, 2023, 23(7): 638-642.
[13]	魏俊吉. 神经外科重症医学规范化诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(6): 477-478.
[14]	杜倩, 邓素君, 邹姗, 金珺, 周青山. 宏基因组第二代测序技术在重症中枢神经系统感染中的应用[J]. 中国现代神经疾病杂志, 2023, 23(6): 479-484.
[15]	曲鑫, 赵浩, 尚峰, 王宁. 神经重症目标温度管理[J]. 中国现代神经疾病杂志, 2023, 23(6): 485-489.

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 脑胶质瘤免疫检查点抑制剂及其临床研究进展

Advance of immune checkpoint inhibitors and clinical trials in glioma

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价