Microenvironmental clues for glioma immunotherapy

Current Neurology and Neuroscience Reports

Volumn 14, Issue 4, 2014, Pages

  Platten, Michael ^a,b   Ochs, Katharina ^a,b   Lemke, Dieter ^a,b   Opitz, Christiane ^a,b   Wick, Wolfgang ^a,b  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Aryl hydrocarbon receptor; Cytotoxic T lymphocyte antigen 4; Indoleamine 2,3 dioxygenase; Kynurenine; Programmed cell death protein 1; Tryptophan; Tryptophan 2,3 dioxygenase

Indexed keywords

AMP 224; BEVACIZUMAB; BMS 936559; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GALUNISERTIB; GLYCOPROTEIN GP 100; INCB 024360; INDOLEAMINE 2,3 DIOXYGENASE; INDOLEAMINE 2,3 DIOXYGENASE INHIBITOR; INDOXIMOD; IPILIMUMAB; KYNURENINE; LAMBROLIZUMAB; LOMUSTINE; MK 3475; MONOCLONAL ANTIBODY; MPDL 3280 A; MPDL 3280A; NIVOLUMAB; OXYGENASE INHIBITOR; PIDILIZUMAB; PLACEBO; PROCARBAZINE; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; TEMOZOLOMIDE; TICILIMUMAB; TRABEDERSEN; TRANSFORMING GROWTH FACTOR BETA; TRYPTOPHAN 2,3 DIOXYGENASE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINCRISTINE;

AMINO ACID METABOLISM; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; DRUG EFFICACY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG TARGETING; GLIOBLASTOMA; HUMAN; IMMUNE DEFICIENCY; IMMUNOMODULATION; IMMUNOSTIMULATION; KIDNEY CARCINOMA; LUNG SMALL CELL CANCER; MELANOMA; OVERALL SURVIVAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SOLID TUMOR; TUMOR MICROENVIRONMENT; ANIMAL; BRAIN; BRAIN TUMOR; GLIOMA; IMMUNOLOGY; IMMUNOTHERAPY; PHYSIOLOGY;

ANIMALS; BRAIN; BRAIN NEOPLASMS; GLIOMA; HUMANS; IMMUNOTHERAPY; TUMOR MICROENVIRONMENT;

EID: 84894754747     PISSN: 15284042     EISSN: 15346293     Source Type: Journal    
DOI: 10.1007/s11910-014-0440-1     Document Type: Review

References (121)

1. Abou-Ghazal M, Yang DS, Qiao W, et al. The incidence, correlation with tumor-infiltrating inflammation, and prognosis of phosphorylated STAT3 expression in human gliomas. Clin Cancer Res. 2008;14:8228-35.
2. Adams S, Braidy N, Bessede A, et al. The kynurenine pathway in brain tumor pathogenesis. Cancer Res. 2012;72:5649-57.
3. Azaro A, Baselga J, Sepulveda JM, et al. The oral transforming growth factor-beta (TGF-β) receptor I kinase inhibitor LY2157299 plus lomustine in patients with treatment-refractory malignant glioma: the first human dose study. J Clin Oncol. 2012;30(15 Suppl):2042.
4. Badawy AA, Evans M. The mechanism of inhibition of rat liver tryptophan pyrrolase activity by 4-hydroxypyrazolo (3,4-d) pyrimidine (Allopurinol). Biochem J. 1973;133:585-91.
5. Barua NU, Gill SS, Love S. Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations. Brain Pathol. 2013. doi:10.1111/bpa.12082.
6. Batchelor TT, Platten M, Palmer-Toy DE, et al. Chorea as a paraneoplastic complication of Hodgkin's disease. J Neurooncol. 1998;36:185-90. (Pubitemid 28073675)
7. Beatty GL, O'Dwyer PJ, Clark J, et al. Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the oral inhibitor of indoleamine 2,3-dioxygenase (IDO1) INCB024360 in patients (pts) with advanced malignancies. J Clin Oncol. 2013;31(15):3025.
8. Beltrami S, Gordon J. Immune surveillance and response to JC virus infection and PML. J Neurovirol. 2013. doi:10.1007/s13365-013-0222-6.
9. Bloch O, Crane CA, Kaur R, et al. Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res. 2013;19:3165-75.
10. Bogdahn U, Hau P, Stockhammer G, et al. Targeted therapy for high-grade glioma with the TGF-B2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro-Oncology. 2011;13:132-42.
11. Bournazou E, Bromberg J. Targeting the tumor microenvironment: JAK-STAT3 signaling. JAK-STAT. 2013;2:e23828.
12. Braun DP, Penn RD, Flannery AM, et al. Immunoregulatory cell function in peripheral blood leukocytes of patients with intracranial gliomas. Neurosurgery. 1982;10:203-9. (Pubitemid 12184609)
13. Burzyn D, Benoist C, Mathis D. Regulatory T cells in nonlymphoid tissues. Nat Immunol. 2013;14:1007-13.
14. Carpentier AF, Brandes AA, Kesari S, et al. Safety interim data from a three-arm phase II study evaluating safety and pharmacokinetics of the oral transforming growth factor-beta (TGF-â) receptor I kinase inhibitor LY2157299 monohydrate in patients with glioblastoma at first progression. J Clin Oncol. 2013;31(15 Suppl):2061.
15. Castriconi R, Daga A, Dondero A, et al. NK cells recognize and kill human glioblastoma cells with stem cell-like properties. J Immunol. 2009;182:3530-9.
16. Ceeraz S, Nowak EC, Noelle RJ. B7 family checkpoint regulators in immune regulation and disease. Trends Immunol. 2013;34:556-63.
17. Charles NA, Holland EC, Gilbertson R, et al. The brain tumor microenvironment. Glia. 2011;59:1169-80.
18. Chen J, Mckay RM, Parada LF. Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell. 2012;149:36-47.
19. Crane CA, Ahn BJ, Han SJ, et al. Soluble factors secreted by glioblastoma cell lines facilitate recruitment, survival, and expansion of regulatory Tcells: implications for immunotherapy. Neuro- Oncology. 2012;14:584-95.
20. Da Fonseca AC, Badie B. Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies. Clin Dev Immunol. 2013;2013:264124.
21. Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014. doi:10.1172/JCI67313.
22. Di Tomaso T, Mazzoleni S, Wang E, et al. Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clin Cancer Res. 2010;16:800-13.
23. Dietrich PY, Dutoit V, Tran Thang NN, et al. T-cell immunotherapy for malignant glioma: toward a combined approach. Curr Opin Oncol. 2010;22:604-10.
24. Donson AM, Birks DK, Schittone SA, et al. Increased immune gene expression and immune cell infiltration in high-grade astrocytoma distinguish long-term from short-term survivors. J Immunol. 2012;189:1920-7.
25. Fan QW, Cheng CK, Gustafson WC, et al. EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma. Cancer Cell. 2013;24:438-49.
26. Fecci PE, Ochiai H, Mitchell DA, 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. (Pubitemid 46649886)
27. Friese MA, Platten M, Lutz SZ, et al. MICA/NKG2D-mediated immunogene therapy of experimental gliomas. Cancer Res. 2003;63:8996-9006. (Pubitemid 38064081)
28. Friese MA, Wischhusen J, Wick W, et al. RNA interference targeting transforming growth factor-β enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo. Cancer Res. 2004;64:7596-603. (Pubitemid 39372105)
29. Fujita M, Kohanbash G, Fellows-Mayle W, et al. COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res. 2011;71:2664-74.
30. Galea I, Bechmann I, Perry VH. What is immune privilege (not)? Trends Immunol. 2007;28:12-8. (Pubitemid 44960159)
31. Gately MK, Glaser M, Dick SJ, et al. In vitro studies on the cell-mediated immune response to human brain tumors. I. Requirement for third-party stimulator lymphocytes in the induction of cell-mediated cytotoxic responses to allogeneic cultured gliomas. J Natl Cancer Inst. 1982;69:1245-54. (Pubitemid 13177515)
32. Gerosa MA, Olivi A, Rosenblum ML, et al. Impaired immuno-competence in patients with malignant gliomas: the possible role of Tg-lymphocyte subpopulations. Neurosurgery. 1982;10:571-3. (Pubitemid 12116739)
33. Gilbert MR, Gonzalez J, Hunter K, et al. A phase I factorial design study of dose-dense temozolomide alone and in combination with thalidomide, isotretinoin, and/or celecoxib as postchemoradiation adjuvant therapy for newly diagnosed glioblastoma. Neuro-Oncology. 2010;12:1167-72.
34. Glas M, Coch C, Trageser D, et al. Targeting the cytosolic innate immune receptors RIG-I and MDA5 effectively counteracts cancer cell heterogeneity in glioblastoma. Stem Cells. 2013;31:1064-74.
35. Grauer OM, Nierkens S, Bennink E, et al. CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int J Cancer. 2007;121:95-105. (Pubitemid 46753856)
36. Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312:117-21.
37. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369:134-44.
38. Heimberger AB. The therapeutic potential of inhibitors of the signal transducer and activator of transcription 3 for central nervous system malignancies. Surg Neurol Int. 2011;2:163.
39. •• Hodi FS, O'Day SJ, Mcdermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711-23. This presents the first evidence from a phase 3 clinical trial that a passive immunotherapy is sufficient to achieve a clinical meaningful antitumor immunity.
40. Holmgaard RB, Zamarin D, Munn DH, et al. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013;210:1389-402.
41. Hussain SF, Kong LY, Jordan J, et al. A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res. 2007;67:9630-6. (Pubitemid 47621208)
42. Jackson E, Dees EC, Kauh JS, et al. A phase I study of indoximod in combination with docetaxel in metastatic solid tumors. J Clin Oncol. 2013;31(15 Suppl):3026.
43. Jacobs SK, Wilson DJ, Melin G, et al. Interleukin-2 and lymphokine activated killer (LAK) cells in the treatment of malignant glioma: clinical and experimental studies. Neurol Res. 1986;8:81-7. (Pubitemid 16098556)
44. Jacobs JF, Idema AJ, Bol KF, et al. Prognostic significance and mechanism of Treg infiltration in human brain tumors. J Neuroimmunol. 2010;225:195-9.
45. Kim YH, Jung TY, Jung S, et al. Tumour-infiltrating T-cell subpopulations in glioblastomas. Br J Neurosurg. 2012;26: 21-7.
46. Kmiecik J, Poli A, Brons NH, et al. Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. J Neuroimmunol. 2013;264:71-83.
47. Kohanbash G, Mckaveney K, Sakaki M, et al. GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid cells through interleukin-4 receptor-α. Cancer Res. 2013;73: 6413-23.
48. 2inhibits the generation of lymphokine-activated killer (LAK) cells. Int J Cancer. 1988;42:562-7.
49. Lanz TV, Becker S, Osswald M, et al. Protein kinase Cβ as a therapeutic target stabilizing blood-brain barrier disruption in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2013;111(1):409-14.
50. Leitlein J, Aulwurm S, Waltereit R, et al. Processing of immunosuppressive pro-TGF-β1,2 by human glioblastoma cells involves cytoplasmic and secreted furin-like proteases. J Immunol. 2001;166:7238-43. (Pubitemid 32525597)
51. Lemke D, Pfenning PN, Sahm F, et al. Costimulatory protein 4IgB7H3 drives the malignant phenotype of glioblastoma by mediating immune escape and invasiveness. Clin Cancer Res. 2012;18:105-17.
52. Levy NL, Mahaley Jr MS, Day ED. In vitro demonstration of cell-mediated immunity to human brain tumors. Cancer Res. 1972;32: 477-82.
53. Liu Y, Carlsson R, Ambjorn M, et al. PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients. J Neurosci. 2013;33:14231-45.
54. Lohr J, Ratliff T, Huppertz A, et al. Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-β. Clin Cancer Res. 2011;17:4296-308.
55. Maes W, Verschuere T, Van Hoylandt A, et al. Depletion of regulatory T cells in a mouse experimental glioma model through anti-CD25 treatment results in the infiltration of non-immunosuppressive myeloid cells in the brain. Clin Dev Immunol. 2013;2013:952469.
56. • Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13:459-65. This is an important study that demonstrates that passive immunotherapy is safe and effective in brain tumors.
57. Mittelbronn M, Platten M, Zeiner P, et al. Macrophage migration inhibitory factor (MIF) expression in human malignant gliomas contributes to immune escape and tumour progression. Acta Neuropathol. 2011;122:353-65.
58. Muller AJ, Duhadaway JB, Donover PS, et al. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med. 2005;11:312-9. (Pubitemid 40460560)
59. Muller AC, Dairam A, Limson JL, et al. Mechanisms by which acyclovir reduces the oxidative neurotoxicity and biosynthesis of quinolinic acid. Life Sci. 2007;80:918-25. (Pubitemid 46186426)
60. Munn DH. Blocking IDO, activity to enhance anti-tumor immunity. Front Biosci (Elite Ed). 2012;4:734-45.
61. Munn DH, Mellor AL. IDO and tolerance to tumors. Trends Mol Med. 2004;10:15-8. (Pubitemid 38165324)
62. Newton RC, Scherle PA, Bowman K, et al. Pharmacodynamic assessment of INCB024360, an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), in advanced cancer patients. J Clin Oncol. 2012;30(15 Suppl):2500.
63. Ochs K, Sahm F, Opitz CA, et al. Immature mesenchymal stem cell-like pericytes as mediators of immunosuppression in human malignant glioma. J Neuroimmunol. 2013;265(1-2):106-16.
64. Opitz CA, Litzenburger UM, Lutz C, et al. Toll-like receptor engagement enhances the immunosuppressive properties of human bone marrow-derived mesenchymal stem cells by inducing indoleamine-2,3-dioxygenase-1 via interferon-β and protein kinase R. Stem Cells. 2009;27:909-19.
65. Opitz CA, Litzenburger UM, Opitz U, et al. The indoleamine-2,3- dioxygenase (IDO) inhibitor 1-methyl-D-tryptophan upregulates IDO1 in human cancer cells. PLoS One. 2011;6:e19823.
66. Opitz CA, Litzenburger UM, Sahm F, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature. 2011;This was the first study to demonstrate that kynurenine is a physiologically relevant ligand of the aryl hydrocarbon receptor, uncovering a novel immunosuppressive pathway in gliomas:197-203.
67. Pantouris G, Mowat CG. Antitumour agents as inhibitors of tryptophan 2,3-dioxygenase. Biochem Biophys Res Commun. 2014;443:28-31.
68. Parsa AT, Waldron JS, Panner A, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2007;13:84-8. (Pubitemid 46067390)
69. Pfenning PN,Weiler M, Merz C, et al.Abstract LB-382: inhibition of CD95 signalling by APG-101 enhances efficacy of radiotherapy (RT) and reduces RT-induced tumor satellite formation. Cancer Res. 2011;71, LB-382.
70. Pilotte L, Larrieu P, Stroobant V, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A. 2012;109(7):2497-502.
71. Platten M, Steinman L. Multiple sclerosis: trapped in deadly glue. Nat Med. 2005;11:252-3. (Pubitemid 40460548)
72. 3 integrin expression. Biochem Biophys Res Commun. 2000;268:607-11.
73. Platten M, Wick W, Weller M. Malignant glioma biology: role for TGF-β in growth, motility, angiogenesis, and immune escape. Microsc Res Tech. 2001;52:401-10. (Pubitemid 32167828)
74. Platten M, Wild-Bode C, Wick W, et al . N -[3,4-Dimethoxycinnamoyl]- anthranilic acid (tranilast) inhibits transforming growth factor-beta release and reduces migration and invasiveness of human malignant glioma cells. Int J Cancer. 2001;93:53-61.
75. Platten M, Kretz A, Naumann U, et al. Monocyte chemoattractant protein-1 increases microglial infiltration and aggressiveness of gliomas. Ann Neurol. 2003;54:388-92.
76. • Platten M, Wick W, Van Den Eynde B. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res. 2012;72:1-6. This review summarizes the mechanisms and relevance of tryptophan catabolism in cancer.
77. Prendergast GC. Cancer: why tumours eat tryptophan. Nature. 2011;478:192-4.
78. Prosniak M, Harshyne LA, Andrews DW, et al. Glioma grade is associated with the accumulation and activity of cells bearing M2 monocyte markers. Clin Cancer Res. 2013;19:3776-86.
79. Pyonteck SM, Akkari L, Schuhmacher AJ, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013;19:1264-72.
80. Raychaudhuri B, Rayman P, Ireland J, et al. Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma. Neuro-Oncology. 2011;13:591-9.
81. Ribas A, Kefford R, Marshall MA, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol. 2013;31:616-22.
82. Ridley A, Cavanagh JB. Lymphocytic infiltration in gliomas: evidence of possible host resistance. Brain. 1971;94:117-24.
83. Rodon Ahnert J, Baselga J, Calvo E, et al. First human dose (FHD) study of the oral transforming growth factor-beta receptor I kinase inhibitor LY2157299 in patients with treatment-refractory malignant glioma. J Clin Oncol. 2011;29(15 Suppl):3011.
84. Roth P, Aulwurm S, Gekel I, et al. Regeneration and tolerance factor: a novel mediator of glioblastoma-associated immunosuppression. Cancer Res. 2006;66:3852-8.
85. Roth P, Mittelbronn M, Wick W, et al. Malignant glioma cells counteract antitumor immune responses through expression of lectin-like transcript-1. Cancer Res. 2007;67:3540-4. (Pubitemid 46762134)
86. Sahm F, Oezen I, Opitz CA, et al. The endogenous tryptophan metabolite and NAD+ precursor quinolinic acid confers resistance of gliomas to oxidative stress. Cancer Res. 2013;73(11):3225-34.
87. Sampson JH, Schmittling RJ, Archer GE, et al. A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma. PLoS One. 2012;7:e31046.
88. Sawamura Y, Hosokawa M, Kuppner MC, et al. Antitumor activity and surface phenotypes of human glioma-infiltrating lymphocytes after in vitro expansion in the presence of interleukin 2. Cancer Res. 1989;49:1843-9. (Pubitemid 19108414)
89. Smith C, Chang MY, Parker KH, et al. IDO Is a nodal pathogenic driver of lung cancer and metastasis development. Cancer Discov. 2012;2(8):722-35.
90. + T cells present in the human brain. Acta Neuropathol. 2013;126: 525-35.
91. Soliman HH, Neuger A, Noyes D, et al. A phase I study of 1-methyl-D-tryptophan in patients with advanced malignancies. J Clin Oncol. 2012;30(15 Suppl):2501.
92. Soliman HH, Minton SE, Han HS, et al. A phase I study of ad.p53 DC vaccine in combination with indoximod in metastatic solid tumors. J Clin Oncol. 2013;31(15 Suppl):3069.
93. Suarez C, Rodon J, Desjardins A, et al. Phase Ib study evaluating safety and pharmacokinetics (PK) of the oral transforming growth factor-beta (TGF-β) receptor I kinase inhibitor LY2157299 monohydrate (LY) when combined with chemoradiotherapy in newly diagnosed malignant gliomas. J Clin Oncol. 2013;31(15 Suppl):2039.
94. Tran Thang NN, Derouazi M, Philippin G, et al. Immune infiltration of spontaneous mouse astrocytomas is dominated by immunosuppressive cells from early stages of tumor development. Cancer Res. 2010;70:4829-39.
95. Tran TT, Uhl M, Ma JY, et al. Inhibiting TGF-β signaling restores immune surveillance in the SMA-560 glioma model. Neuro- Oncology. 2007;9:259-70. (Pubitemid 47169658)
96. Ueda R, Fujita M, Zhu X, et al. Systemic inhibition of transforming growth factor-β in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Clin Cancer Res. 2009;15:6551-9.
97. Uhl M, Aulwurm S, Wischhusen J, et al. SD-208, a novel transforming growth factor β receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004;64: 7954-61. (Pubitemid 39446929)
98. Umansky V, Sevko A. Tumor microenvironment and myeloid-derived suppressor cells. Cancer Microenviron. 2013;6:169-77.
99. Uyttenhove C, Pilotte L, Theate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269-74. (Pubitemid 37279849)
100. Vom Berg J, Vrohlings M, Haller S, et al. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma rejection. J Exp Med. 2013;210:2803-11.
101. Wainwright DA, Sengupta S, Han Y, et al. Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors. Neuro-Oncology. 2011;13:1308-23.
102. Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of Tcell responses.Nat Rev Immunol. 2011;11: 852-63.
103. Wang Y, Ait-Oufella H, Herbin O, et al. TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice. J Clin Invest. 2010;120:422 - 32.
104. Wang X, Crowe PJ, Goldstein D, et al. STAT3 inhibition, a novel approach to enhancing targeted therapy in human cancers (review). Int J Oncol. 2012;41:1181-91.
105. Weber JS, Kudchadkar RR, Yu B, et al. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol. 2013;31:4311-8.
106. Wei J, Barr J, Kong LY, et al. Glioma-associated cancer-initiating cells induce immunosuppression. Clin Cancer Res. 2010;16:461-73.
107. Wei J,Wang F, Kong LY, et al. miR-124 inhibits STAT3 signaling to enhance T cell-mediated immune clearance of glioma. Cancer Res. 2013;73:3913-26.
108. Wei B, Wang L, Zhao X, et al. The upregulation of programmed death 1 on peripheral blood T cells of glioma is correlated with disease progression. Tumour Biol. 2013. doi:10.1007/s13277-013-1376-9.
109. Weiler M, Hartmann C, Wiewrodt D, et al. Chemoradiotherapy of newly diagnosed glioblastoma with intensified temozolomide. Int J Radiat Oncol Biol Phys. 2010;77:670-6.
110. Wick W, Weller M. Trabedersen to target transforming growth factor-β: when the journey is not the reward, in reference to Bogdahn et al. (Neuro-Oncology 2011;13:132- 142). Neuro- Oncology. 2011;13:559-60. author reply 561-2.
111. Wick W, Platten M, Weller M. Glioma cell invasion: regulation of metalloproteinase activity by TGF-β. J Neurooncol. 2001;53:177-85. (Pubitemid 33034690)
112. Wick W, Naumann U, Weller M. Transforming growth factor-β: a molecular target for the future therapy of glioblastoma. Curr Pharm Des. 2006;12:341-9.
113. Wiencke JK, Accomando WP, Zheng S, et al. Epigenetic biomarkers of T-cells in human glioma. Epigenetics. 2012;7:1391-402.
114. Wilmotte R, Burkhardt K, Kindler V, et al. B7-homolog 1 expression by human glioma: a new mechanism of immune evasion. Neuroreport. 2005;16:1081-5. (Pubitemid 41017610)
115. Wintterle S, Schreiner B, Mitsdoerffer M, et al. Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res. 2003;63:7462-7.
116. • Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369: 122-33. This was the first study to demonstrate safety and efficacy of combined anti-CTLA4 and anti-PD-1 therapy.
117. Wood GW, Morantz RA. Depressed T lymphocyte function in brain tumor patients:monocytes as suppressor cells. J Neurooncol. 1983;1:87-94. (Pubitemid 13000329)
118. Wrann M, Bodmer S, De Martin R, et al. T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. EMBO J. 1987;6:1633-6.
119. Yao Y, Tao R, Wang X, et al. B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells. Neuro-Oncology. 2009;11:757-66.
120. Zeng J, See AP, Phallen 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.
121. Zhang M, Kleber S, Rohrich M, et al. Blockade of TGF-β signaling by the TGFßR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Res. 2011;71:7155-67.