Immune Evasion Strategies of Glioblastoma

Frontiers in Surgery

Volumn 3, Issue , 2016, Pages

  Razavi, Seyed Mostafa ^a   Lee, Karen E ^a   Jin, Benjamin E ^a   Aujla, Parvir S ^a   Gholamin, Sharareh ^a   Li, Gordon ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

cancer immunotherapy; glioblastoma; immune evasion; immune system; immunosuppression

Indexed keywords

EID: 84985941767     PISSN: None     EISSN: 2296875X     Source Type: Journal    
DOI: 10.3389/fsurg.2016.00011     Document Type: Review

References (126)

1. Xu LW, Chow KKH, Lim M, Li G. Current vaccine trials in glioblastoma: a review. J Immunol Res (2014) 2014:796856.10.1155/2014/79685624804271
2. Ampie L, Woolf EC, Dardis C. Immunotherapeutic advancements for glioblastoma. Front Oncol (2015) 5:12.10.3389/fonc.2015.0001225688335
3. Johnson DR, O’Neill BP. Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol (2012) 107:359–64.10.1007/s11060-011-0749-422045118
4. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJB, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol (2009) 10:459–66.10.1016/S1470-2045(09)70025-7
5. Thomas RP, Xu LW, Lober RM, Li G, Nagpal S. The incidence and significance of multiple lesions in glioblastoma. J Neurooncol (2013) 112:91–7.10.1007/s11060-012-1030-123354652
6. Louveau A, Harris TH, Kipnis J. Revisiting the mechanisms of CNS immune privilege. Trends Immunol (2015) 36:569–77.10.1016/j.it.2015.08.00626431936
7. Forrester JV, Xu H, Lambe T, Cornall R. Immune privilege or privileged immunity? Mucosal Immunol (2008) 1:372–81.10.1038/mi.2008.2719079201
8. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature (2015) 523:337–41.10.1038/nature1443226030524
9. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med (2015) 212:991–9.10.1084/jem.2014229026077718
10. Owens T, Bechmann I, Engelhardt B. Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol (2008) 67:1113–21.10.1097/NEN.0b013e31818f9ca819018243
11. Chow BW, Gu C. The molecular constituents of the blood-brain barrier. Trends Neurosci (2015) 38:598–608.10.1016/j.tins.2015.08.00326442694
12. Hao C, Parney IF, Roa WH, Turner J, Petruk KC, Ramsay DA. Cytokine and cytokine receptor mRNA expression in human glioblastomas: evidence of Th1, Th2 and Th3 cytokine dysregulation. Acta Neuropathol (2002) 103:171–8.10.1007/s00401010044811810184
13. Rodrigues JC, Gonzalez GC, Zhang L, Ibrahim G, Kelly JJ, Gustafson MP, et al. Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties. Neuro Oncol (2010) 12:351–65.10.1093/neuonc/nop02320308313
14. Jackson C, Ruzevick J, Phallen J, Belcaid Z, Lim M. Challenges in immunotherapy presented by the glioblastoma multiforme microenvironment. Clin Dev Immunol (2011) 2011:732413–20.10.1155/2011/73241322190972
15. Mittal SK, Roche PA. Suppression of antigen presentation by IL-10. Curr Opin Immunol (2015) 34:22–7.10.1016/j.coi.2014.12.00925597442
16. Trifunović J, Miller L, Debeljak Ž, Horvat V. Pathologic patterns of interleukin 10 expression – a review. Biochem Med (Zagreb) (2015) 25:36–48.10.11613/BM.2015.004
17. Huettner C, Paulus W, Roggendorf W. Messenger RNA expression of the immunosuppressive cytokine IL-10 in human gliomas. Am J Pathol (1995) 146:317–22.7856743
18. Huettner C, Czub S, Kerkau S, Roggendorf W, Tonn JC. Interleukin 10 is expressed in human gliomas in vivo and increases glioma cell proliferation and motility in vitro. Anticancer Res (1997) 17:3217–24.9413151
19. Van Meir EG. Cytokines and tumors of the central nervous system. Glia (1995) 15:264–88.10.1002/glia.4401503088586463
20. Strle K, Zhou JH, Shen WH, Broussard SR, Johnson RW, Freund GG, et al. Interleukin-10 in the brain. Crit Rev Immunol (2001) 21:427–49.10.1615/CritRevImmunol.v21.i5.20
21. Fontana A, Bodmer S, Frei K, Malipiero U, Siepl C. Expression of TGF-beta 2 in human glioblastoma: a role in resistance to immune rejection? Ciba Found Symp (1991) 157:232–8.1649035
22. Tritschler I, Gramatzki D, Capper D, Mittelbronn M, Meyermann R, Saharinen J, et al. Modulation of TGF-beta activity by latent TGF-beta-binding protein 1 in human malignant glioma cells. Int J Cancer (2009) 125:530–40.10.1002/ijc.2444319431147
23. Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci (2003) 116:217–24.10.1242/jcs.0022912482908
24. Kirkbride KC, Blobe GC. Inhibiting the TGF-beta signalling pathway as a means of cancer immunotherapy. Expert Opin Biol Ther (2003) 3:251–61.10.1517/14712598.3.2.25112662140
25. Sheng KC, Wright MD, Apostolopoulos V. Inflammatory mediators hold the key to dendritic cell suppression and tumor progression. Curr Med Chem (2011) 18:5507–18.10.2174/09298671179834720722172061
26. Ghiringhelli F, Puig PE, Roux S, Parcellier A, Schmitt E, Solary E, et al. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med (2005) 202:919–29.10.1084/jem.2005046316186184
27. Whiteside TL, Mandapathil M, Schuler P. The role of the adenosinergic pathway in immunosuppression mediated by human regulatory T cells (Treg). Curr Med Chem (2011) 18:5217–23.10.1007/s00262-010-0924-z22087822
28. Couldwell WT, Dore-Duffy P, Apuzzo ML, Antel JP. Malignant glioma modulation of immune function: relative contribution of different soluble factors. J Neuroimmunol (1991) 33:89–96.10.1016/0165-5728(91)90052-92066398
29. Dix AR, Brooks WH, Roszman TL, Morford LA. Immune defects observed in patients with primary malignant brain tumors. J Neuroimmunol (1999) 100:216–32.10.1016/S0165-5728(99)00203-910695732
30. Wischhusen J, Jung G, Radovanovic I, Beier C, Steinbach JP, Rimner A, et al. Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma. Cancer Res (2002) 62:2592–9.11980654
31. Chahlavi A, Rayman P, Richmond AL, Biswas K, Zhang R, Vogelbaum M, et al. Glioblastomas induce T-lymphocyte death by two distinct pathways involving gangliosides and CD70. Cancer Res (2005) 65:5428–38.10.1158/0008-5472.CAN-04-439515958592
32. Badie B, Schartner J, Prabakaran S, Paul J, Vorpahl J. Expression of Fas ligand by microglia: possible role in glioma immune evasion. J Neuroimmunol (2001) 120:19–24.10.1016/S0165-5728(01)00361-711694315
33. Walker DG, Chuah T, Rist MJ, Pender MP. T-cell apoptosis in human glioblastoma multiforme: implications for immunotherapy. J Neuroimmunol (2006) 175:59–68.10.1016/j.jneuroim.2006.03.00616631933
34. Wei J, Wu A, Kong L-Y, Wang Y, Fuller G, Fokt I, et al. Hypoxia potentiates glioma-mediated immunosuppression. PLoS One (2011) 6:e16195.10.1371/journal.pone.001619521283755
35. Lin EY, Li J-F, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, et al. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res (2006) 66:11238–46.10.1158/0008-5472.CAN-06-127817114237
36. Wu A, Wei J, Kong L-Y, Wang Y, Priebe W, Qiao W, et al. Glioma cancer stem cells induce immunosuppressive macrophages/microglia. Neuro Oncol (2010) 12:1113–25.10.1093/neuonc/noq08220667896
37. Magnus T, Schreiner B, Korn T, Jack C, Guo H, Antel J, et al. Microglial expression of the B7 family member B7 homolog 1 confers strong immune inhibition: implications for immune responses and autoimmunity in the CNS. J Neurosci (2005) 25:2537–46.10.1523/JNEUROSCI.4794-04.200515758163
38. Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med (2007) 13:84–8.10.1038/nm151717159987
39. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med (2002) 8:793–800.10.1038/nm73012091876
40. Lipson EJ, Forde PM, Hammers H-J, Emens LA, Taube JM, Topalian SL. Antagonists of PD-1 and PD-L1 in cancer treatment. Semin Oncol (2015) 42:587–600.10.1053/j.seminoncol.2015.05.01326320063
41. Wilmotte R, Burkhardt K, Kindler V, Belkouch M-C, Dussex G, Tribolet Nd, et al. B7-homolog 1 expression by human glioma: a new mechanism of immune evasion. Neuroreport (2005) 16:1081–5.10.1097/00001756-200507130-0001015973152
42. Wei B, Wang L, Zhao X, Du C, Guo Y, Sun Z. The upregulation of programmed death 1 on peripheral blood T cells of glioma is correlated with disease progression. Tumour Biol (2014) 35:2923–9.10.1007/s13277-013-1376-924375192
43. Bloch O, Crane CA, Kaur R, Safaee M, Rutkowski MJ, Parsa AT. Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res (2013) 19:3165–75.10.1158/1078-0432.CCR-12-331423613317
44. Fecci PE, Ochiai H, Mitchell DA, Grossi PM, Sweeney AE, Archer GE, et al. Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function. Clin Cancer Res (2007) 13:2158–67.10.1158/1078-0432.CCR-06-207017404100
45. Belcaid Z, Phallen JA, Zeng J, See AP, Mathios D, Gottschalk C, et al. Focal radiation therapy combined with 4-1BB activation and CTLA-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model. PLoS One (2014) 9:e101764.10.1371/journal.pone.010176425013914
46. Jordan JT, Sun W, Hussain SF, DeAngulo G, Prabhu SS, Heimberger AB. Preferential migration of regulatory T cells mediated by glioma-secreted chemokines can be blocked with chemotherapy. Cancer Immunol Immunother (2008) 57:123–31.10.1007/s00262-007-0336-x17522861
47. Desbaillets I, Tada M, de Tribolet N, Diserens AC, Hamou MF, Van Meir EG. Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro. Int J Cancer (1994) 58:240–7.10.1002/ijc.29105802167517920
48. Crane CA, Ahn BJ, Han SJ, Parsa AT. Soluble factors secreted by glioblastoma cell lines facilitate recruitment, survival, and expansion of regulatory T cells: implications for immunotherapy. Neuro Oncol (2012) 14:584–95.10.1093/neuonc/nos01422406925
49. Coniglio SJ, Eugenin E, Dobrenis K, Stanley ER, West BL, Symons MH, et al. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med (2012) 18:519–27.10.2119/molmed.2011.0021722294205
50. Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med (2013) 19:1264–72.10.1038/nm.333724056773
51. Zhang L, Liu W, Alizadeh D, Zhao D, Farrukh O, Lin J, et al. S100B attenuates microglia activation in gliomas: possible role of STAT3 pathway. Glia (2011) 59:486–98.10.1002/glia.2111821264954
52. Markovic DS, Vinnakota K, Chirasani S, Synowitz M, Raguet H, Stock K, et al. Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci USA (2009) 106:12530–5.10.1073/pnas.080427310619617536
53. Camara-Quintana JQ, Nitta RT, Li G. Pathology: commonly monitored glioblastoma markers: EFGR, EGFRvIII, PTEN, and MGMT. Neurosurg Clin N Am (2012) 23:237–46.10.1016/j.nec.2012.01.01122440867
54. Zhang J, Sarkar S, Cua R, Zhou Y, Hader W, Yong VW. A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis. Carcinogenesis (2012) 33:312–9.10.1093/carcin/bgr28922159219
55. Lin H-C, Song T-Y, Hu M-L. S-adenosylhomocysteine promotes the invasion of C6 glioma cells via increased secretion of matrix metalloproteinase-2 in murine microglial BV2 cells. Toxicol Sci (2009) 112:322–30.10.1093/toxsci/kfp21819770485
56. Kerber M, Reiss Y, Wickersheim A, Jugold M, Kiessling F, Heil M, et al. Flt-1 signaling in macrophages promotes glioma growth in vivo. Cancer Res (2008) 68:7342–51.10.1158/0008-5472.CAN-07-624118794121
57. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med (2014) 370:709–22.10.1056/NEJMoa130834524552318
58. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med (2014) 370:699–708.10.1056/NEJMoa130857324552317
59. Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, et al. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol (2008) 10:10–8.10.1215/15228517-2007-03517951512
60. Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R. Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol (2008) 116:79–86.10.1007/s00401-008-0359-118351367
61. Chang WLW, Baumgarth N, Yu D, Barry PA. Human cytomegalovirus-encoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality. J Virol (2004) 78:8720–31.10.1128/JVI.78.16.8720-8731.200415280480
62. Spencer JV, Lockridge KM, Barry PA, Lin G, Tsang M, Penfold MET, et al. Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10. J Virol (2002) 76:1285–92.10.1128/JVI.76.3.1285-1292.200211773404
63. Dziurzynski K, Wei J, Qiao W, Hatiboglu MA, Kong L-Y, Wu A, et al. Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin Cancer Res (2011) 17:4642–9.10.1158/1078-0432.CCR-11-041421490182
64. Gorbachev AV, Kobayashi H, Kudo D, Tannenbaum CS, Finke JH, Shu S, et al. CXC chemokine ligand 9/monokine induced by IFN-gamma production by tumor cells is critical for T cell-mediated suppression of cutaneous tumors. J Immunol (2007) 178:2278–86.10.4049/jimmunol.178.4.227817277133
65. Calzascia T, Masson F, Di Berardino-Besson W, Contassot E, Wilmotte R, Aurrand-Lions M, et al. Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs. Immunity (2005) 22:175–84.10.1016/j.immuni.2004.12.00815723806
66. Cserr HF, Harling-Berg CJ, Knopf PM. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol (1992) 2:269–76.10.1111/j.1750-3639.1992.tb00703.x1341962
67. Ohtsuki S, Terasaki T. Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development. Pharm Res (2007) 24:1745–58.10.1007/s11095-007-9374-517619998
68. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol (2007) 7:715–25.10.1038/nri215517703228
69. D’Agostino PM, Gottfried-Blackmore A, Anandasabapathy N, Bulloch K. Brain dendritic cells: biology and pathology. Acta Neuropathol (2012) 124:599–614.10.1007/s00401-012-1018-022825593
70. Bechmann I, Galea I, Perry VH. What is the blood-brain barrier (not)? Trends Immunol (2007) 28:5–11.10.1016/j.it.2006.11.00717140851
71. Mohammad MG, Tsai VWW, Ruitenberg MJ, Hassanpour M, Li H, Hart PH, et al. Immune cell trafficking from the brain maintains CNS immune tolerance. J Clin Invest (2014) 124:1228–41.10.1172/JCI7154424569378
72. Engelhardt B, Ransohoff RM. Capture, crawl, cross: the T cell code to breach the blood-brain barriers. Trends Immunol (2012) 33:579–89.10.1016/j.it.2012.07.00422926201
73. Prins RM, Soto H, Konkankit V, Odesa SK, Eskin A, Yong WH, 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) 17:1603–15.10.1158/1078-0432.CCR-10-256321135147
74. Prins RM, Wang X, Soto H, Young E, Lisiero DN, Fong B, et al. Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. J Immunother (2013) 36:152–7.10.1097/CJI.0b013e3182811ae423377664
75. Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol (2012) 12:557–69.10.1038/nri325422790179
76. McDonnell AM, Robinson BWS, Currie AJ. Tumor antigen cross-presentation and the dendritic cell: where it all begins? Clin Dev Immunol (2010) 2010:539519.10.1155/2010/53951920976125
77. Jarry U, Jeannin P, Pineau L, Donnou S, Delneste Y, Couez D. Efficiently stimulated adult microglia cross-prime naive CD8+ T cells injected in the brain. Eur J Immunol (2013) 43:1173–84.10.1002/eji.20124304023529826
78. Flügel A, Labeur MS, Grasbon-Frodl EM, Kreutzberg GW, Graeber MB. Microglia only weakly present glioma antigen to cytotoxic T cells. Int J Dev Neurosci (1999) 17:547–56.10.1016/S0736-5748(99)00020-910571416
79. Graeber MB, Scheithauer BW, Kreutzberg GW. Microglia in brain tumors. Glia (2002) 40:252–9.10.1002/glia.1014712379912
80. Kjellman C, Olofsson SP, Hansson O, Schantz Von T, Lindvall M, Nilsson I, et al. Expression of TGF-beta isoforms, TGF-beta receptors, and SMAD molecules at different stages of human glioma. Int J Cancer (2000) 89:251–8.10.1002/1097-0215(20000520)89:3<251:AID-IJC7>3.0.CO;2-510861501
81. Mieczkowski J, Kocyk M, Nauman P, Gabrusiewicz K, Sielska MG, Przanowski P, et al. Down-regulation of IKKβ expression in glioma-infiltrating microglia/macrophages is associated with defective inflammatory/immune gene responses in glioblastoma. Oncotarget (2015) 6(32):33077–90.10.18632/oncotarget.531026427514
82. Schartner JM, Hagar AR, Van Handel M, Zhang L, Nadkarni N, Badie B. Impaired capacity for upregulation of MHC class II in tumor-associated microglia. Glia (2005) 51:279–85.10.1002/glia.2020115818597
83. Badie B, Bartley B, Schartner J. Differential expression of MHC class II and B7 costimulatory molecules by microglia in rodent gliomas. J Neuroimmunol (2002) 133:39–45.10.1016/S0165-5728(02)00350-812446006
84. Kostianovsky AM, Maier LM, Anderson RC, Bruce JN, Anderson DE. Astrocytic regulation of human monocytic/microglial activation. J Immunol (2008) 181:5425–32.10.4049/jimmunol.181.8.542518832699
85. Beauvillain C, Donnou S, Jarry U, Scotet M, Gascan H, Delneste Y, et al. Neonatal and adult microglia cross-present exogenous antigens. Glia (2008) 56:69–77.10.1002/glia.2056517932942
86. Lasky JL, Panosyan EH, Plant A, Davidson T, Yong WH, Prins RM, et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas. Anticancer Res (2013) 33:2047–56.23645755
87. Sakai K, Shimodaira S, Maejima S, Udagawa N, Sano K, Higuchi Y, et al. Dendritic cell-based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma. J Neurosurg (2015) 123:989–97.10.3171/2015.1.JNS14155426252465
88. Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol (2002) 196:254–65.10.1002/path.102711857487
89. Morimura T, Neuchrist C, Kitz K, Budka H, Scheiner O, Kraft D, et al. Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation. Acta Neuropathol (1990) 80:287–94.10.1007/BF002946472399810
90. Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol (2006) 177:7303–11.10.4049/jimmunol.177.10.730317082649
91. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol (2010) 11:889–96.10.1038/ni.193720856220
92. Tseng D, Volkmer J-P, Willingham SB, Contreras-Trujillo H, Fathman JW, Fernhoff NB, et al. Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response. Proc Natl Acad Sci USA (2013) 110:11103–8.10.1073/pnas.130556911023690610
93. Hussain SF, Yang D, Suki D, Aldape K, Grimm E, Heimberger AB. The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro Oncol (2006) 8:261–79.10.1215/15228517-2006-00816775224
94. Randolph GJ, Jakubzick C, Qu C. Antigen presentation by monocytes and monocyte-derived cells. Curr Opin Immunol (2008) 20:52–60.10.1016/j.coi.2007.10.01018160272
95. Carrasco YR, Batista FD. B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node. Immunity (2007) 27:160–71.10.1016/j.immuni.2007.06.00717658276
96. Hon H, Oran A, Brocker T, Jacob J. B lymphocytes participate in cross-presentation of antigen following gene gun vaccination. J Immunol (2005) 174:5233–42.10.4049/jimmunol.174.9.523315843519
97. Clark MR, Massenburg D, Siemasko K, Hou P, Zhang M. B-cell antigen receptor signaling requirements for targeting antigen to the MHC class II presentation pathway. Curr Opin Immunol (2004) 16:382–7.10.1016/j.coi.2004.03.00715134789
98. Candolfi M, Curtin JF, Yagiz K, Assi H, Wibowo MK, Alzadeh GE, et al. B cells are critical to T-cell-mediated antitumor immunity induced by a combined immune-stimulatory/conditionally cytotoxic therapy for glioblastoma. Neoplasia (2011) 13:947–60.10.1593/neo.1102422028620
99. Okamoto Y, Yamashita J, Hasegawa M, Fujisawa H, Yamashima T, Hashimoto T, et al. Cervical lymph nodes play the role of regional lymph nodes in brain tumour immunity in rats. Neuropathol Appl Neurobiol (1999) 25:113–22.10.1046/j.1365-2990.1999.00165.x10215999
100. Laman JD, Weller RO. Drainage of cells and soluble antigen from the CNS to regional lymph nodes. J Neuroimmune Pharmacol (2013) 8:840–56.10.1007/s11481-013-9470-823695293
101. Waziri A. Glioblastoma-derived mechanisms of systemic immunosuppression. Neurosurg Clin N Am (2010) 21:31–42.10.1016/j.nec.2009.08.00519944964
102. Gustafson MP, Lin Y, New KC, Bulur PA, O’Neill BP, Gastineau DA, et al. Systemic immune suppression in glioblastoma: the interplay between CD14+HLA-DRlo/neg monocytes, tumor factors, and dexamethasone. Neuro Oncol (2010) 12:631–44.10.1093/neuonc/noq00120179016
103. Kahlon KS, Brown C, Cooper LJN, Raubitschek A, Forman SJ, Jensen MC. Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells. Cancer Res (2004) 64:9160–6.10.1158/0008-5472.CAN-04-045415604287
104. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell (2015) 27:450–61.10.1016/j.ccell.2015.03.00125858804
105. Nduom EK, Wei J, Yaghi NK, Huang N, Kong L-Y, Gabrusiewicz K, et al. PD-L1 expression and prognostic impact in glioblastoma. Neuro Oncol (2016) 18(2):195–205.10.1093/neuonc/nov17226323609
106. Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys (2013) 86:343–9.10.1016/j.ijrobp.2012.12.02523462419
107. Tang X, Li Q, Zhu Y, Zheng D, Dai J, Ni W, et al. The advantages of PD1 activating chimeric receptor (PD1-ACR) engineered lymphocytes for PDL1(+) cancer therapy. Am J Transl Res (2015) 7:460–73.26045887
108. Whiteside TL. Induced regulatory T cells in inhibitory microenvironments created by cancer. Expert Opin Biol Ther (2014) 14:1411–25.10.1517/14712598.2014.92743224934899
109. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol (2006) 6:295–307.10.1038/nri180616557261
110. Brusko TM, Putnam AL, Bluestone JA. Human regulatory T cells: role in autoimmune disease and therapeutic opportunities. Immunol Rev (2008) 223:371–90.10.1111/j.1600-065X.2008.00637.x18613848
111. Elliott LH, Brooks WH, Roszman TL. Activation of immunoregulatory lymphocytes obtained from patients with malignant gliomas. J Neurosurg (1987) 67:231–6.10.3171/jns.1987.67.2.02312885402
112. Heimberger AB, Abou-Ghazal M, Reina-Ortiz C, Yang DS, Sun W, Qiao W, et al. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin Cancer Res (2008) 14:5166–72.10.1158/1078-0432.CCR-08-032018698034
113. Waziri A, Killory B, Ogden AT, Canoll P, Anderson RCE, Kent SC, et al. Preferential in situ CD4+CD56+ T cell activation and expansion within human glioblastoma. J Immunol (2008) 180:7673–80.10.4049/jimmunol.180.11.767318490770
114. Ebert LM, Tan BS, Browning J, Svobodova S, Russell SE, Kirkpatrick N, et al. The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells. Cancer Res (2008) 68:3001–9.10.1158/0008-5472.CAN-07-566418413770
115. Wainwright DA, Nigam P, Thaci B, Dey M, Lesniak MS. Recent developments on immunotherapy for brain cancer. Expert Opin Emerg Drugs (2012) 17:181–202.10.1517/14728214.2012.67992922533851
116. Jacobs JFM, Idema AJ, Bol KF, Grotenhuis JA, de Vries IJM, Wesseling P, et al. Prognostic significance and mechanism of Treg infiltration in human brain tumors. J Neuroimmunol (2010) 225:195–9.10.1016/j.jneuroim.2010.05.02020537408
117. Ford AL, Goodsall AL, Hickey WF, Sedgwick JD. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J Immunol (1995) 154:4309–21.7722289
118. Badie B, Schartner JM. Flow cytometric characterization of tumor-associated macrophages in experimental gliomas. Neurosurgery (2000) 46:957–61.10.1097/00006123-200004000-0003510764271
119. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer (2004) 4:71–8.10.1038/nrc1256
120. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res (2006) 66:605–12.10.1158/0008-5472.CAN-05-400516423985
121. Siveen KS, Kuttan G. Role of macrophages in tumour progression. Immunol Lett (2009) 123:97–102.10.1016/j.imlet.2009.02.01119428556
122. da Fonseca AC, Badie B. Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies. Clin Dev Immunol (2013) 2013:264124–5.10.1155/2013/26412423864876
123. Badie B, Schartner J, Klaver J, Vorpahl J. In vitro modulation of microglia motility by glioma cells is mediated by hepatocyte growth factor/scatter factor. Neurosurgery (1999) 44:1077–82.10.1097/00006123-199905000-0007510232541
124. Held-Feindt J, Hattermann K, Müerköster SS, Wedderkopp H, Knerlich-Lukoschus F, Ungefroren H, et al. CX3CR1 promotes recruitment of human glioma-infiltrating microglia/macrophages (GIMs). Exp Cell Res (2010) 316:1553–66.10.1016/j.yexcr.2010.02.01820184883
125. Wesolowska A, Kwiatkowska A, Slomnicki L, Dembinski M, Master A, Sliwa M, et al. Microglia-derived TGF-beta as an important regulator of glioblastoma invasion – an inhibition of TGF-beta-dependent effects by shRNA against human TGF-beta type II receptor. Oncogene (2008) 27:918–30.10.1038/sj.onc.1210683
126. Glass R, Synowitz M. CNS macrophages and peripheral myeloid cells in brain tumours. Acta Neuropathol (2014) 128:347–62.10.1007/s00401-014-1274-224722970