Embracing rejection: Immunologic trends in brain metastasis

References

• Dunn GP, Fecci PE, Curry WT. Cancer immunoediting in malignant glioma. Neurosurgery 2012; 71:201-22; PMID:22353795; http://dx.doi.org/10.1227/NEU.0b013e31824f840d
   PubMed Web of Science ®Google Scholar
• Gallego Perez-Larraya J, Hildebrand J. Brain metastases. Handb Clin Neurol 2014; 121:1143-57; PMID:24365409; http://dx.doi.org/10.1016/B978-0-7020-4088-7.00077-8
   PubMedGoogle Scholar
• Ranjan T, Abrey LE. Current management of metastatic brain disease. Neurotherapeutics 2009; 6:598-603; PMID:19560748; http://dx.doi.org/10.1016/j.nurt.2009.04.012
   PubMed Web of Science ®Google Scholar
• Lu-Emerson C, Eichler AF. Brain metastases. Continuum 2012; 18:295-311; PMID:22810128
   PubMedGoogle Scholar
• Chan AW, Loeffler JS. Controversies in the management of patients with brain metastases. Cancer J. 2001; 7:105-7; PMID:11324762
   PubMed Web of Science ®Google Scholar
• Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011; 29:134-41; PMID:21041710; http://dx.doi.org/10.1200/JCO.2010.30.1655
   PubMed Web of Science ®Google Scholar
• Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009; 10:1037-44; PMID:19801201; http://dx.doi.org/10.1016/S1470-2045(09)70263-3
   PubMed Web of Science ®Google Scholar
• Mitchell DA, Fecci PE, Sampson JH. Immunotherapy of malignant brain tumors. Immunol Rev. 2008; 222:70-100; PMID:18363995; http://dx.doi.org/10.1111/j.1600-065X.2008.00603.x
   PubMed Web of Science ®Google Scholar
• Gedeon PC, Riccione KA, Fecci PE, Sampson JH. Antibody-based immunotherapy for malignant glioma. Semin Oncol. 2014; 41:496-510; PMID:25173142; http://dx.doi.org/10.1053/j.seminoncol.2014.06.004
   PubMed Web of Science ®Google Scholar
• Medawar PB. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol. 1948; 29:58-69; PMID:18865105
   PubMed Web of Science ®Google Scholar
• Hamilton A, Sibson NR. Role of the systemic immune system in brain metastasis. Mol Cell Neurosci. 2013; 53:42-51; PMID:23073146; http://dx.doi.org/10.1016/j.mcn.2012.10.004
   PubMed Web of Science ®Google Scholar
• Woodworth GF, Dunn GP, Nance EA, Hanes J, Brem H. Emerging insights into barriers to effective brain tumor therapeutics. Front Oncol. 2014; 4:126; PMID:25101239; http://dx.doi.org/10.3389/fonc.2014.00126
   PubMedGoogle Scholar
• Winkler EA, Bell RD, Zlokovic BV. Central nervous system pericytes in health and disease. Nat Neurosci. 2011; 14:1398-405; PMID:22030551; http://dx.doi.org/10.1038/nn.2946
   PubMed Web of Science ®Google Scholar
• Pardridge WM. The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2005; 2:3-14; PMID:15717053; http://dx.doi.org/10.1602/neurorx.2.1.3
   PubMedGoogle Scholar
• Groothuis DR, Vavra MW, Schlageter KE, Kang EW, Itskovich AC, Hertzler S, Allen CV, Lipton HL. Efflux of drugs and solutes from brain: the interactive roles of diffusional transcapillary transport, bulk flow and capillary transporters. J Cereb Blood Flow Metab 2007; 27:43-56; PMID:16639426; http://dx.doi.org/10.1038/sj.jcbfm.9600315
   PubMed Web of Science ®Google Scholar
• Brightman MW, Klatzo I, Olsson Y, Reese TS. The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci. 1970; 10:215-39; PMID:4909727; http://dx.doi.org/10.1016/0022-510X(70)90151-6
   PubMed Web of Science ®Google Scholar
• Pollay M, Roberts PA. Blood-brain barrier: a definition of normal and altered function. Neurosurgery 1980; 6:675-85; PMID:7001265; http://dx.doi.org/10.1227/00006123-198006000-00014
   PubMed Web of Science ®Google Scholar
• Sjogren AM, Thelestam M, Blomqvist L, Linda H, Remahl S, Risling M. Extravasation of staphylococcal alpha-toxin in normal and injured CNS regions lacking blood-brain barrier function: observations after ventral root replantation. Brain Res. 1991; 559:276-82; PMID:1794101; http://dx.doi.org/10.1016/0006-8993(91)90012-K
   PubMed Web of Science ®Google Scholar
• d'Avella D, Cicciarello R, Albiero F, Mesiti M, Gagliardi ME, Russi E, d'Aquino A, Tomasello F, d'Aquino S. Quantitative study of blood-brain barrier permeability changes after experimental whole-brain radiation. Neurosurgery 1992; 30:30-4; PMID:1738452; http://dx.doi.org/10.1227/00006123-199201000-00006
   PubMed Web of Science ®Google Scholar
• Wilhelm I, Molnar J, Fazakas C, Hasko J, Krizbai IA. Role of the blood-brain barrier in the formation of brain metastases. Int J Molecular Sci. 2013; 14:1383-411; PMID:23344048; http://dx.doi.org/10.3390/ijms14011383
   PubMed Web of Science ®Google Scholar
• Owens T, Renno T, Taupin V, Krakowski M. Inflammatory cytokines in the brain: does the CNS shape immune responses?. Immunol Today 1994; 15:566-71; PMID:7848517; http://dx.doi.org/10.1016/0167-5699(94)90218-6
   PubMedGoogle Scholar
• Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today 1992; 13:507-12; PMID:1463583; http://dx.doi.org/10.1016/0167-5699(92)90027-5
   PubMedGoogle Scholar
• 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; PMID:1341962; http://dx.doi.org/10.1111/j.1750-3639.1992.tb00703.x
   PubMed Web of Science ®Google Scholar
• Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS et al. Structural and functional features of central nervous system lymphatic vessels. Nature 2015; 523:337-41; PMID:26030524
   PubMed Web of Science ®Google Scholar
• Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, Wiig H, Alitalo K. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015; 212:991-9; PMID:26077718; http://dx.doi.org/10.1084/jem.20142290
   PubMed Web of Science ®Google Scholar
• Lorger M, Felding-Habermann B. Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis. Am J Pathol. 2010; 176:2958-71; PMID:20382702; http://dx.doi.org/10.2353/ajpath.2010.090838
   PubMed Web of Science ®Google Scholar
• Lorger M, Lee H, Forsyth JS, Felding-Habermann B. Comparison of in vitro and in vivo approaches to studying brain colonization by breast cancer cells. J Neuro-oncol. 2011; 104:689-96; PMID:21359851; http://dx.doi.org/10.1007/s11060-011-0550-4
   PubMed Web of Science ®Google Scholar
• Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006; 12:895-904; PMID:16892035; http://dx.doi.org/10.1038/nm1469
   PubMed Web of Science ®Google Scholar
• Gorantla V, Kirkwood JM, Tawbi HA. Melanoma brain metastases: an unmet challenge in the era of active therapy. Curr Oncol Rep. 2013; 15:483-91; PMID:23954973; http://dx.doi.org/10.1007/s11912-013-0335-3
   PubMed Web of Science ®Google Scholar
• Brayton J, Qing Z, Hart MN, VanGilder JC, Fabry Z. Influence of adhesion molecule expression by human brain microvessel endothelium on cancer cell adhesion. J Neuroimmunol 1998; 89:104-12; PMID:9726832; http://dx.doi.org/10.1016/S0165-5728(98)00127-1
   PubMed Web of Science ®Google Scholar
• Barthel SR, Gavino JD, Descheny L, Dimitroff CJ. Targeting selectins and selectin ligands in inflammation and cancer. Expert opinion on therapeutic targets 2007; 11:1473-91; PMID:18028011; http://dx.doi.org/10.1517/14728222.11.11.1473
   PubMed Web of Science ®Google Scholar
• Kusters B, Westphal JR, Smits D, Ruiter DJ, Wesseling P, Keilholz U, de Waal RM. The pattern of metastasis of human melanoma to the central nervous system is not influenced by integrin alpha(v)beta(3) expression. Int J of Cancer Journal international du cancer 2001; 92:176-80; PMID:11291042; http://dx.doi.org/10.1002/1097-0215(200102)9999:9999%3c::AID-IJC1173%3e3.0.CO;2-L
   PubMed Web of Science ®Google Scholar
• Serres S, Soto MS, Hamilton A, McAteer MA, Carbonell WS, Robson MD, Ansorge O, Khrapitchev A, Bristow C, Balathasan L et al. Molecular MRI enables early and sensitive detection of brain metastases. Proc Natl Acad Sci USA. 2012; 109:6674-9; PMID:22451897; http://dx.doi.org/10.1073/pnas.1117412109
   PubMed Web of Science ®Google Scholar
• Fidler IJ, Yano S, Zhang RD, Fujimaki T, Bucana CD. The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol. 2002; 3:53-7; PMID:11905606; http://dx.doi.org/10.1016/S1470-2045(01)00622-2
   PubMed Web of Science ®Google Scholar
• On NH, Mitchell R, Savant SD, Bachmeier CJ, Hatch GM, Miller DW. Examination of blood-brain barrier (BBB) integrity in a mouse brain tumor model. J Neuro-oncol. 2013; 111:133-43; PMID:23184143; http://dx.doi.org/10.1007/s11060-012-1006-1
   PubMed Web of Science ®Google Scholar
• Lu W, Bucana CD, Schroit AJ. Pathogenesis and vascular integrity of breast cancer brain metastasis. Int J Cancer Journal international du cancer 2007; 120:1023-6; PMID:17187362; http://dx.doi.org/10.1002/ijc.22388
   PubMed Web of Science ®Google Scholar
• Ballinger WE, Jr., Schimpff RD. An experimental model for cerebral metastasis: preliminary light and ultrastructural studies. J Neuropathol Exp Neurol 1979; 38:19-34; PMID:430105; http://dx.doi.org/10.1097/00005072-197901000-00003
   PubMed Web of Science ®Google Scholar
• Kawaguchi T, Tobai S, Nakamura K. Extravascular migration of tumor cells in the brain: an electron microscopic study. Invasion metastasis 1982; 2:40-50; PMID:7188390
   PubMedGoogle Scholar
• Paku S, Dome B, Toth R, Timar J. Organ-specificity of the extravasation process: an ultrastructural study. Clin Exp Metastasis 2000; 18:481-92; PMID:11592305; http://dx.doi.org/10.1023/A:1011858925376
   PubMed Web of Science ®Google Scholar
• Gerstner ER, Fine RL. Increased permeability of the blood-brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm. J Clin Oncol. 2007; 25:2306-12; PMID:17538177; http://dx.doi.org/10.1200/JCO.2006.10.0677
   PubMed Web of Science ®Google Scholar
• Adkins CE, Mohammad AS, Terrell-Hall TB, Dolan EL, Shah N, Sechrest E, Griffith J, Lockman PR. Characterization of passive permeability at the blood-tumor barrier in five preclinical models of brain metastases of breast cancer. Clin Exp Metastasis 2016; 33:373-83; PMID:26944053
   PubMed Web of Science ®Google Scholar
• Lockman PR, Mittapalli RK, Taskar KS, Rudraraju V, Gril B, Bohn KA, Adkins CE, Roberts A, Thorsheim HR, Gaasch JA et al. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res. 2010; 16:5664-78; PMID:20829328; http://dx.doi.org/10.1158/1078-0432.CCR-10-1564
   PubMed Web of Science ®Google Scholar
• Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert WE, Goldbrunner R, Herms J, Winkler F. Real-time imaging reveals the single steps of brain metastasis formation. Nat Med. 2010; 16:116-22; PMID:20023634; http://dx.doi.org/10.1038/nm.2072
   PubMed Web of Science ®Google Scholar
• Fazakas C, Wilhelm I, Nagyoszi P, Farkas AE, Hasko J, Molnar J, Bauer H, Bauer HC, Ayaydin F, Dung NT et al. Transmigration of melanoma cells through the blood-brain barrier: role of endothelial tight junctions and melanoma-released serine proteases. PloS One 2011; 6:e20758; PMID:21674054
   PubMed Web of Science ®Google Scholar
• Carbonell WS, Ansorge O, Sibson N, Muschel R. The vascular basement membrane as “soil” in brain metastasis. PloS One 2009; 4:e5857; PMID:19516901; http://dx.doi.org/10.1371/journal.pone.0005857
   PubMed Web of Science ®Google Scholar
• Fan J, Cai B, Zeng M, Hao Y, Giancotti FG, Fu BM. Integrin beta4 signaling promotes mammary tumor cell adhesion to brain microvascular endothelium by inducing ErbB2-mediated secretion of VEGF. Ann Biomed Eng. 2011; 39:2223-41; PMID:21556948; http://dx.doi.org/10.1007/s10439-011-0321-6
   PubMed Web of Science ®Google Scholar
• Kusters B, Leenders WP, Wesseling P, Smits D, Verrijp K, Ruiter DJ, Peters JP, van Der Kogel AJ, de Waal RM. Vascular endothelial growth factor-A(165) induces progression of melanoma brain metastases without induction of sprouting angiogenesis. Cancer Res. 2002; 62:341-5; PMID:11809675
   PubMed Web of Science ®Google Scholar
• Kusters B, de Waal RM, Wesseling P, Verrijp K, Maass C, Heerschap A, Barentsz JO, Sweep F, Ruiter DJ, Leenders WP. Differential effects of vascular endothelial growth factor A isoforms in a mouse brain metastasis model of human melanoma. Cancer Res. 2003; 63:5408-13; PMID:14500375
   PubMed Web of Science ®Google Scholar
• Xie TX, Huang FJ, Aldape KD, Kang SH, Liu M, Gershenwald JE, Xie K, Sawaya R, Huang S. Activation of stat3 in human melanoma promotes brain metastasis. Cancer Res. 2006; 66:3188-96; PMID:16540670; http://dx.doi.org/10.1158/0008-5472.CAN-05-2674
   PubMed Web of Science ®Google Scholar
• Leenders WP, Kusters B, Verrijp K, Maass C, Wesseling P, Heerschap A, Ruiter D, Ryan A, de Waal R. Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor progression via vessel co-option. Clin Cancer Res. 2004; 10:6222-30; PMID:15448011; http://dx.doi.org/10.1158/1078-0432.CCR-04-0823
   PubMed Web of Science ®Google Scholar
• Kim LS, Huang S, Lu W, Lev DC, Price JE. Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice. Clin Exp Metastasis 2004; 21:107-18; PMID:15168728; http://dx.doi.org/10.1023/B:CLIN.0000024761.00373.55
   PubMed Web of Science ®Google Scholar
• Wu PF, Lin CH, Kuo CH, Chen WW, Yeh DC, Liao HW, Huang SM, Cheng AL, Lu YS. A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis. BMC Cancer 2015; 15:299; PMID:25928457; http://dx.doi.org/10.1186/s12885-015-1290-1
   PubMed Web of Science ®Google Scholar
• Dunn GP, Dunn IF, Curry WT. Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immun. 2007; 7:12; PMID:17691714
   PubMedGoogle Scholar
• Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA et al. Genes that mediate breast cancer metastasis to the brain. Nature 2009; 459:1005-9; PMID:19421193; http://dx.doi.org/10.1038/nature08021
   PubMed Web of Science ®Google Scholar
• Izraely S, Sagi-Assif O, Klein A, Meshel T, Tsarfaty G, Pasmanik-Chor M, Nahmias C, Couraud PO, Ateh E, Bryant JL et al. The metastatic microenvironment: brain-residing melanoma metastasis and dormant micrometastasis. Int J Cancer 2012; 131:1071-82; PMID:22025079; http://dx.doi.org/10.1002/ijc.27324
   PubMed Web of Science ®Google Scholar
• Ridgway LD, Wetzel MD, Marchetti D. Modulation of GEF-H1 induced signaling by heparanase in brain metastatic melanoma cells. J Cell Biochem 2010; 111:1299-309; PMID:20803552; http://dx.doi.org/10.1002/jcb.22854
   PubMed Web of Science ®Google Scholar
• Marchetti D, Li J, Shen R. Astrocytes contribute to the brain-metastatic specificity of melanoma cells by producing heparanase. Cancer Res. 2000; 60:4767-70; PMID:10987284
   PubMed Web of Science ®Google Scholar
• Lin Q, Balasubramanian K, Fan D, Kim SJ, Guo L, Wang H, Bar-Eli M, Aldape KD, Fidler IJ. Reactive astrocytes protect melanoma cells from chemotherapy by sequestering intracellular calcium through gap junction communication channels. Neoplasia 2010; 12:748-54; PMID:20824051; http://dx.doi.org/10.1593/neo.10602
   PubMed Web of Science ®Google Scholar
• Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH, Lee DJ, Chaft JE, Kris MG, Huse JT, Brogi E et al. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 2014; 156:1002-16; PMID:24581498; http://dx.doi.org/10.1016/j.cell.2014.01.040
   PubMed Web of Science ®Google Scholar
• Brantley EC, Guo L, Zhang C, Lin Q, Yokoi K, Langley RR, Kruzel E, Maya M, Kim SW, Kim SJ et al. Nitric oxide-mediated tumoricidal activity of murine microglial cells. Transl Oncol. 2010; 3:380-8; PMID:21151477; http://dx.doi.org/10.1593/tlo.10208
   PubMed Web of Science ®Google Scholar
• Fitzgerald DP, Palmieri D, Hua E, Hargrave E, Herring JM, Qian Y, Vega-Valle E, Weil RJ, Stark AM, Vortmeyer AO et al. Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization. Clin Exp Metastasis 2008; 25:799-810; PMID:18649117; http://dx.doi.org/10.1007/s10585-008-9193-z
   PubMed Web of Science ®Google Scholar
• Pukrop T, Dehghani F, Chuang HN, Lohaus R, Bayanga K, Heermann S, Regen T, Van Rossum D, Klemm F, Schulz M et al. Microglia promote colonization of brain tissue by breast cancer cells in a Wnt-dependent way. Glia 2010; 58:1477-89; PMID:20549749
   PubMed Web of Science ®Google Scholar
• Wei J, Gabrusiewicz K, Heimberger A. The controversial role of microglia in malignant gliomas. Clin Dev Immunol 2013; 2013:285246; PMID:23983766; http://dx.doi.org/10.1155/2013/285246
   PubMedGoogle Scholar
• He BP, Wang JJ, Zhang X, Wu Y, Wang M, Bay BH, Chang AY. Differential reactions of microglia to brain metastasis of lung cancer. Mol Med. 2006; 12:161-70; PMID:17088948; http://dx.doi.org/10.2119/2006-00033.He
   PubMed Web of Science ®Google Scholar
• Lin EY, Pollard JW. Macrophages: modulators of breast cancer progression. Novartis Found Sym. 2004; 256:158-68; PMID:15027489; http://dx.doi.org/10.1002/0470856734.ch12
   PubMedGoogle Scholar
• Theoharides TC, Rozniecki JJ, Sahagian G, Jocobson S, Kempuraj D, Conti P, Kalogeromitros D. Impact of stress and mast cells on brain metastases. J Neuroimmunol 2008; 205:1-7; PMID:18977036; http://dx.doi.org/10.1016/j.jneuroim.2008.09.014
   PubMed Web of Science ®Google Scholar
• Lu W, Su J, Kim LS, Bucana CD, Donawho C, He J, Fidler IJ, Dong Z. Active specific immunotherapy against occult brain metastasis. Cancer Res. 2003; 63:1345-50; PMID:12649197
   PubMed Web of Science ®Google Scholar
• Fecci PE, Heimberger AB, Sampson JH. Immunotherapy for primary brain tumors: no longer a matter of privilege. Clin Cancer Res. 2014; 20:5620-9; PMID:25398845; http://dx.doi.org/10.1158/1078-0432.CCR-14-0832
   PubMed Web of Science ®Google Scholar
• Rolle CE, Sengupta S, Lesniak MS. Mechanisms of immune evasion by gliomas. Adv Exp Med Biol. 2012; 746:53-76; PMID:22639159; http://dx.doi.org/10.1007/978-1-4614-3146-6_5
   PubMed Web of Science ®Google Scholar
• Brooks WH, Roszman TL, Mahaley MS, Woosley RE. Immunobiology of primary intracranial tumours. II. Analysis of lymphocyte subpopulations in patients with primary brain tumours. Clin Exp Immunol 1977; 29:61-6; PMID:330067
   PubMed Web of Science ®Google Scholar
• Fecci PE, Mitchell DA, Whitesides JF, Xie W, Friedman AH, Archer GE, Herndon JE, 2nd, Bigner DD, Dranoff G, Sampson JH. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 2006; 66:3294-302; PMID:16540683; http://dx.doi.org/10.1158/0008-5472.CAN-05-3773
   PubMed Web of Science ®Google Scholar
• El Andaloussi A, Lesniak MS. An increase in CD4+CD25+FOXP3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme. Neuro-oncology 2006; 8:234-43; PMID:16723631; http://dx.doi.org/10.1215/15228517-2006-006
   PubMed Web of Science ®Google Scholar
• 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. Clin Cancer Res. 2012; 18:6110-21; PMID:22932670; http://dx.doi.org/10.1158/1078-0432.CCR-12-2130
   PubMed Web of Science ®Google Scholar
• Facoetti A, Nano R, Zelini P, Morbini P, Benericetti E, Ceroni M, Campoli M, Ferrone S. Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors. Clin Cancer Res. 2005; 11:8304-11; PMID:16322289; http://dx.doi.org/10.1158/1078-0432.CCR-04-2588
   PubMed Web of Science ®Google Scholar
• Anderson RC, Anderson DE, Elder JB, Brown MD, Mandigo CE, Parsa AT, Goodman RR, McKhann GM, Sisti MB, Bruce JN. Lack of B7 expression, not human leukocyte antigen expression, facilitates immune evasion by human malignant gliomas. Neurosurgery 2007; 60:1129-36; PMID:17538388; http://dx.doi.org/10.1227/01.NEU.0000255460.91892.44
   PubMed Web of Science ®Google Scholar
• Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2007; 13:84-8; PMID:17159987; http://dx.doi.org/10.1038/nm1517
   PubMed Web of Science ®Google Scholar
• Abou-Ghazal M, Yang DS, Qiao W, Reina-Ortiz C, Wei J, Kong LY, Fuller GN, Hiraoka N, Priebe W, Sawaya R 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; PMID:19088040; http://dx.doi.org/10.1158/1078-0432.CCR-08-1329
   PubMed Web of Science ®Google Scholar
• Roussel E, Gingras MC, Grimm EA, Bruner JM, Moser RP. Predominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas. Clin Exp Immunol 1996; 105:344-52; PMID:8706344; http://dx.doi.org/10.1046/j.1365-2249.1996.d01-753.x
   PubMed Web of Science ®Google Scholar
• Friese MA, Platten M, Lutz SZ, Naumann U, Aulwurm S, Bischof F, Buhring HJ, Dichgans J, Rammensee HG, Steinle A et al. MICA/NKG2D-mediated immunogene therapy of experimental gliomas. Cancer Res. 2003; 63:8996-9006; PMID:14695218
   PubMed Web of Science ®Google Scholar
• Eisele G, Wischhusen J, Mittelbronn M, Meyermann R, Waldhauer I, Steinle A, Weller M, Friese MA. TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells. Brain 2006; 129:2416-25; PMID:16891318; http://dx.doi.org/10.1093/brain/awl205
   PubMed Web of Science ®Google Scholar
• Wischhusen J, Friese MA, Mittelbronn M, Meyermann R, Weller M. HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo. J Neuropathol Exp Neurol 2005; 64:523-8; PMID:15977644; http://dx.doi.org/10.1093/jnen/64.6.523
   PubMed Web of Science ®Google Scholar
• Wherry EJ. T cell exhaustion. Nat Immunol 2011; 12:492-9; PMID:21739672; http://dx.doi.org/10.1038/ni.2035
   PubMed Web of Science ®Google Scholar
• Sugihara AQ, Rolle CE, Lesniak MS. Regulatory T cells actively infiltrate metastatic brain tumors. Int J Oncol. 2009; 34:1533-40; PMID:19424570
   PubMed Web of Science ®Google Scholar
• Berghoff AS, Ricken G, Widhalm G, Rajky O, Dieckmann K, Birner P, Bartsch R, Holler C, Preusser M. Tumour-infiltrating lymphocytes and expression of programmed death ligand 1 (PD-L1) in melanoma brain metastases. Histopathology 2015; 66:289-99; PMID:25314639; http://dx.doi.org/10.1111/his.12537
   PubMed Web of Science ®Google Scholar
• Harter PN, Bernatz S, Scholz A, Zeiner PS, Zinke J, Kiyose M, Blasel S, Beschorner R, Senft C, Bender B et al. Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases. Oncotarget 2015; 6:40836-49; PMID:26517811
   PubMed Web of Science ®Google Scholar
• Kluger HM, Zito CR, Barr ML, Baine MK, Chiang VL, Sznol M, Rimm DL, Chen L, Jilaveanu LB. Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites. Clin Cancer Res. 2015; 21:3052-60; PMID:25788491; http://dx.doi.org/10.1158/1078-0432.CCR-14-3073
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012; 366:2443-54; PMID:22658127; http://dx.doi.org/10.1056/NEJMoa1200690
   PubMed Web of Science ®Google Scholar
• Stadler S, Weina K, Gebhardt C, Utikal J. New therapeutic options for advanced non-resectable malignant melanoma. Adv Med Sci. 2015; 60:83-8; PMID:25596540; http://dx.doi.org/10.1016/j.advms.2014.12.002
   PubMed Web of Science ®Google Scholar
• Masson F, Calzascia T, Di Berardino-Besson W, de Tribolet N, Dietrich PY, Walker PR. Brain microenvironment promotes the final functional maturation of tumor-specific effector CD8+ T cells. J Immunol 2007; 179:845-53; PMID:NOT_FOUND; http://dx.doi.org/10.4049/jimmunol.179.2.845
   PubMed Web of Science ®Google Scholar
• Nishimura F, Dusak JE, Eguchi J, Zhu X, Gambotto A, Storkus WJ, Okada H. Adoptive transfer of type 1 CTL mediates effective anti-central nervous system tumor response: critical roles of IFN-inducible protein-10. Cancer Res. 2006; 66:4478-87; PMID:16618775; http://dx.doi.org/10.1158/0008-5472.CAN-05-3825
   PubMed Web of Science ®Google Scholar
• Sasaki K, Zhu X, Vasquez C, Nishimura F, Dusak JE, Huang J, Fujita M, Wesa A, Potter DM, Walker PR et al. Preferential expression of very late antigen-4 on type 1 CTL cells plays a critical role in trafficking into central nervous system tumors. Cancer Res. 2007; 67:6451-8; PMID:17616706; http://dx.doi.org/10.1158/0008-5472.CAN-06-3280
   PubMed Web of Science ®Google Scholar
• Sharma P, Allison JP. The future of immune checkpoint therapy. Science 2015; 348:56-61; PMID:25838373; http://dx.doi.org/10.1126/science.aaa8172
   PubMed Web of Science ®Google Scholar
• Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363:711-23; PMID:20525992; http://dx.doi.org/10.1056/NEJMoa1003466
   PubMed Web of Science ®Google Scholar
• Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015; 33:1889-94; PMID:25667295; http://dx.doi.org/10.1200/JCO.2014.56.2736
   PubMed Web of Science ®Google Scholar
• Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012; 13:459-65; PMID:22456429; http://dx.doi.org/10.1016/S1470-2045(12)70090-6
   PubMed Web of Science ®Google Scholar
• Queirolo P, Spagnolo F, Ascierto PA, Simeone E, Marchetti P, Scoppola A, Del Vecchio M, Di Guardo L, Maio M, Di Giacomo AM et al. Efficacy and safety of ipilimumab in patients with advanced melanoma and brain metastases. J Neuro-oncol. 2014; 118:109-16; PMID:24532241
   PubMed Web of Science ®Google Scholar
• Sunshine J, Taube JM. PD-1/PD-L1 inhibitors. Curr Opin Pharmacol 2015; 23:32-8; PMID:26047524; http://dx.doi.org/10.1016/j.coph.2015.05.011
   PubMed Web of Science ®Google Scholar
• Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015; 372:2006-17; PMID:25891304; http://dx.doi.org/10.1056/NEJMoa1414428
   PubMed Web of Science ®Google Scholar
• Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015; 373:23-34; PMID:26027431; http://dx.doi.org/10.1056/NEJMoa1504030
   PubMed Web of Science ®Google Scholar
• Di Giacomo AM, Ascierto PA, Pilla L, Santinami M, Ferrucci PF, Giannarelli D, Marasco A, Rivoltini L, Simeone E, Nicoletti SV et al. Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol. 2012; 13:879-86; PMID:22894884; http://dx.doi.org/10.1016/S1470-2045(12)70324-8
   PubMed Web of Science ®Google Scholar
• Lonser RR, Song DK, Klapper J, Hagan M, Auh S, Kerr PB, Citrin DE, Heiss JD, Camphausen K, Rosenberg SA. Surgical management of melanoma brain metastases in patients treated with immunotherapy. J Neurosurg 2011; 115:30-6; PMID:21476810; http://dx.doi.org/10.3171/2011.3.JNS091107
   PubMed Web of Science ®Google Scholar
• Patel KR, Lawson DH, Kudchadkar RR, Carthon BC, Oliver DE, Okwan-Duodu D, Ahmed R, Khan MK. Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases. Neuro-oncology 2015; 17:1312-21; PMID:26014049; http://dx.doi.org/10.1093/neuonc/nov093
   PubMed Web of Science ®Google Scholar
• Frey B, Rubner Y, Kulzer L, Werthmoller N, Weiss EM, Fietkau R, Gaipl US. Antitumor immune responses induced by ionizing irradiation and further immune stimulation. Cancer Immunol Immunother 2014; 63:29-36; PMID:24052136; http://dx.doi.org/10.1007/s00262-013-1474-y
   PubMed Web of Science ®Google Scholar
• Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 2009; 114:589-95; PMID:19349616; http://dx.doi.org/10.1182/blood-2009-02-206870
   PubMed Web of Science ®Google Scholar
• Vanpouille-Box C, Pilones KA, Wennerberg E, Formenti SC, Demaria S. In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. Vaccine 2015; 33:7415-22; PMID:26148880
   PubMed Web of Science ®Google Scholar
• Knisely JP, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VL. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg 2012; 117:227-33; PMID:22702482; http://dx.doi.org/10.3171/2012.5.JNS111929
   PubMed Web of Science ®Google Scholar
• Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med. 2013; 2:899-906; PMID:24403263; http://dx.doi.org/10.1002/cam4.140
   PubMed Web of Science ®Google Scholar
• Hong JJ, Rosenberg SA, Dudley ME, Yang JC, White DE, Butman JA, Sherry RM. Successful treatment of melanoma brain metastases with adoptive cell therapy. Clin Cancer Res. 2010; 16:4892-8; PMID:20719934; http://dx.doi.org/10.1158/1078-0432.CCR-10-1507
   PubMed Web of Science ®Google Scholar
• Bedikian AY, Richards J, Kharkevitch D, Atkins MB, Whitman E, Gonzalez R. A phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma. Melanoma Res. 2010; 20:218-26; PMID:20354459
   PubMed Web of Science ®Google Scholar