Brain cancer immunoediting: novel examples provided by immunotherapy of malignant gliomas

References

• Ehrlich P. The Collected Papers of Paul Ehrlich. 3, 302 (1957).
   Google Scholar
• Thomas L. Cellular and Humoral Aspects of Hypersensitivity (1959).
   Google Scholar
• Burnet M. Cancer; a biological approach. I. The processes of control. Br. Med. J.1(5022), 779–786 (1957).
   PubMed Web of Science ®Google Scholar
• Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol.6(11), 836–848 (2006).
   PubMed Web of Science ®Google Scholar
• Koebel CM, Vermi W, Swann JB et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature450(7171), 903–907 (2007).
   PubMed Web of Science ®Google Scholar
• Hochmeister S, Zeitelhofer M, Bauer J et al. After injection into the striatum, in vitro-differentiated microglia- and bone marrow-derived dendritic cells can leave the central nervous system via the blood stream. Am. J. Pathol.173(6), 1669–1681 (2008).
   Google Scholar
• Ransohoff RM, Kivisakk P, Kidd G. Three or more routes for leukocyte migration into the central nervous system. Nat. Rev. Immunol.3(7), 569–581 (2003).
   PubMed Web of Science ®Google Scholar
• Grauer OM, Wesseling P, Adema GJ. Immunotherapy of diffuse gliomas: biological background, current status and future developments. Brain Pathol.19(4), 674–693 (2009).
   PubMedGoogle Scholar
• Dunn GP, Dunn IF, Curry WT. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immunol.7, 12 (2007).
   PubMedGoogle Scholar
• Calzascia T, Masson F, Di Berardino-Besson W et al. Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs. Immunity22(2), 175–184 (2005).
   PubMed Web of Science ®Google Scholar
• Czerniecki BJ, Koski GK, Koldovsky U et al. Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Cancer Res.67(4), 1842–1852 (2007).
   PubMed Web of Science ®Google Scholar
• Wekerle H, Linington C, Lassmann H, Meyermann R. Cellular immune reactivity within the CNS. Trends Neurosci.9, 271–277 (1986).
   Web of Science ®Google Scholar
• Hickey WF, Hsu BL, Kimura H. T-lymphocyte entry into the central nervous system. J. Neurosci. Res.28(2), 254–260 (1991).
   PubMed Web of Science ®Google Scholar
• 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.8(3), 261–279 (2006).
   PubMed Web of Science ®Google Scholar
• Perrin G, Schnuriger V, Quiquerez AL et al. Astrocytoma infiltrating lymphocytes include major T cell clonal expansions confined to the CD8 subset. Int. Immunol.11(8), 1337–1350 (1999).
   PubMedGoogle Scholar
• Von Hanwehr RI, Hofman FM, Taylor CR, Apuzzo ML. Mononuclear lymphoid populations infiltrating the microenvironment of primary CNS tumors. Characterization of cell subsets with monoclonal antibodies. J. Neurosurg.60(6), 1138–1147 (1984).
   PubMedGoogle Scholar
• 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.70(12), 4829–4839 (2010).
   PubMed Web of Science ®Google Scholar
• Goldschneider I, Cone RE. A central role for peripheral dendritic cells in the induction of acquired thymic tolerance. Trends Immunol.24(2), 77–81 (2003).
   Google Scholar
• Lohr J, Ratliff T, Huppertz A et al. Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived transforming growth factor-betas. Clin. Cancer Res.17(13), 4296–4308 (2011).
   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.179(2), 845–853 (2007).
   PubMed Web of Science ®Google Scholar
• Calzascia T, Di Berardino-Besson W, Wilmotte R et al. Cutting edge: cross-presentation as a mechanism for efficient recruitment of tumor-specific CTL to the brain. J. Immunol.171(5), 2187–2191 (2003).
   PubMedGoogle Scholar
• Galea I, Bernardes-Silva M, Forse PA, Van Rooijen N, Liblau RS, Perry VH. An antigen-specific pathway for CD8 T cells across the blood–brain barrier. J. Exp. Med.204(9), 2023–2030 (2007).
   PubMed Web of Science ®Google Scholar
• Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat. Rev. Immunol.6(10), 715–727 (2006).
   PubMed Web of Science ®Google Scholar
• Cresswell AC, Sisley K, Laws D, Parsons MA, Rennie IG, Murray AK. Reduced expression of TAP-1 and TAP-2 in posterior uveal melanoma is associated with progression to metastatic disease. Melanoma Res11(3), 275–281 (2001).
   PubMed Web of Science ®Google Scholar
• Romero JM, Jimenez P, Cabrera T et al. Coordinated downregulation of the antigen presentation machinery and HLA class I/beta2-microglobulin complex is responsible for HLA-ABC loss in bladder cancer. Int. J. Cancer113(4), 605–610 (2005).
   PubMed Web of Science ®Google Scholar
• Satoh E, Mabuchi T, Satoh H, Asahara T, Nukui H, Naganuma H. Reduced expression of the transporter associated with antigen processing 1 molecule in malignant glioma cells, and its restoration by interferon-γ and -β. J. Neurosurg.104(2), 264–271 (2006).
   Google Scholar
• 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. Glia51(4), 279–285 (2005).
   PubMed Web of Science ®Google Scholar
• Badie B, Bartley B, Schartner J. Differential expression of MHC class II and B7 costimulatory molecules by microglia in rodent gliomas. J. Neuroimmunol.133(1–2), 39–45 (2002).
   PubMed Web of Science ®Google Scholar
• Kostianovsky AM, Maier LM, Anderson RC, Bruce JN, Anderson DE. Astrocytic regulation of human monocytic/microglial activation. J. Immunol.181(8), 5425–5432 (2008).
   PubMed Web of Science ®Google Scholar
• Magnus T, Schreiner B, Korn T 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.25(10), 2537–2546 (2005).
   PubMed Web of Science ®Google Scholar
• Badie B, Schartner J, Prabakaran S, Paul J, Vorpahl J. Expression of Fas ligand by microglia: possible role in glioma immune evasion. J. Neuroimmunol.120(1–2), 19–24 (2001).
   PubMed Web of Science ®Google Scholar
• Roszman T, Elliott L, Brooks W. Modulation of T-cell function by gliomas. Immunol. Today12(10), 370–374 (1991).
   PubMedGoogle Scholar
• Bodmer S, Strommer K, Frei K et al. Immunosuppression and transforming growth factor-β in glioblastoma. Preferential production of transforming growth factor-β 2. J. Immunol.143(10), 3222–3229 (1989).
   PubMed Web of Science ®Google Scholar
• Buccoliero AM, Caldarella A, Gheri CF et al. Inducible cyclooxygenase (COX-2) in glioblastoma – clinical and immunohistochemical (COX-2-VEGF) correlations. Clin. Neuropathol.25(2), 59–66 (2006).
   PubMedGoogle Scholar
• Castelli MG, Chiabrando C, Fanelli R et al. Prostaglandin and thromboxane synthesis by human intracranial tumors. Cancer Res.49(6), 1505–1508 (1989).
   PubMed Web of Science ®Google Scholar
• Cobbs CS, Brenman JE, Aldape KD, Bredt DS, Israel MA. Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res.55(4), 727–730 (1995).
   PubMed Web of Science ®Google Scholar
• Nitta T, Hishii M, Sato K, Okumura K. Selective expression of interleukin-10 gene within glioblastoma multiforme. Brain Res.649(1–2), 122–128 (1994).
   PubMed Web of Science ®Google Scholar
• Constam DB, Philipp J, Malipiero UV, Ten Dijke P, Schachner M, Fontana A. Differential expression of transforming growth factor-beta 1, -beta 2, and -beta 3 by glioblastoma cells, astrocytes, and microglia. J. Immunol.148(5), 1404–1410 (1992).
   PubMed Web of Science ®Google Scholar
• Weller M, Constam DB, Malipiero U, Fontana A. Transforming growth factor-beta 2 induces apoptosis of murine T cell clones without down-regulating bcl-2 mRNA expression. Eur. J. Immunol.24(6), 1293–1300 (1994).
   PubMedGoogle Scholar
• Weller M, Fontana A. The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-β, T-cell apoptosis, and the immune privilege of the brain. Brain Res. Rev.21(2), 128–151 (1995).
   PubMed Web of Science ®Google Scholar
• 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.17(5A), 3217–3224 (1997).
   PubMed Web of Science ®Google Scholar
• Hishii M, Nitta T, Ishida H et al. Human glioma-derived interleukin-10 inhibits antitumor immune responses in vitro. Neurosurgery37(6), 1160–1166; discussion 1166–1167 (1995).
   PubMed Web of Science ®Google Scholar
• De Vleeschouwer S, Spencer Lopes I, Ceuppens JL, Van Gool SW. Persistent IL-10 production is required for glioma growth suppressive activity by Th1-directed effector cells after stimulation with tumor lysate-loaded dendritic cells. J. Neurooncol.84(2), 131–140 (2007).
   Google Scholar
• Zagzag D, Salnikow K, Chiriboga L et al. Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain. Lab. Invest.85(3), 328–341 (2005).
   PubMed Web of Science ®Google Scholar
• Wilmotte R, Burkhardt K, Kindler V et al. B7-homolog 1 expression by human glioma: a new mechanism of immune evasion. Neuroreport16(10), 1081–1085 (2005).
   PubMed Web of Science ®Google Scholar
• 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.63(21), 7462–7467 (2003).
   PubMed Web of Science ®Google Scholar
• Parsa AT, Waldron JS, Panner A et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat. Med.13(1), 84–88 (2007).
   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.64(6), 523–528 (2005).
   PubMed Web of Science ®Google Scholar
• Mittelbronn M, Simon P, Loffler C et al. Elevated HLA-E levels in human glioblastomas but not in grade I to III astrocytomas correlate with infiltrating CD8+ cells. J. Neuroimmunol.189(1–2), 50–58 (2007).
   PubMed Web of Science ®Google Scholar
• Facoetti A, Nano R, Zelini P et al. Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors. Clin. Cancer Res.11(23), 8304–8311 (2005).
   PubMed Web of Science ®Google Scholar
• Mehling M, Simon P, Mittelbronn M et al. WHO grade associated downregulation of MHC class I antigen-processing machinery components in human astrocytomas: does it reflect a potential immune escape mechanism? Acta Neuropathol.114(2), 111–119 (2007).
   Google Scholar
• Wei J, Barr J, Kong LY et al. Glioma-associated cancer-initiating cells induce immunosuppression. Clin. Cancer Res.16(2), 461–473 (2010).
   PubMed Web of Science ®Google Scholar
• Fukumori T, Takenaka Y, Yoshii T et al. CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis. Cancer Res.63(23), 8302–8311 (2003).
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Abou-Ghazal M, Reina-Ortiz C et al. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin. Cancer Res.14(16), 5166–5172 (2008).
   PubMed Web of Science ®Google Scholar
• Fecci PE, Sweeney AE, Grossi PM et al. Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells. Clin. Cancer Res.12(14 Pt 1), 4294–4305 (2006).
   PubMed Web of Science ®Google Scholar
• Kim R, Emi M, Tanabe K, Uchida Y, Toge T. The role of Fas ligand and transforming growth factor beta in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy. Cancer100(11), 2281–2291 (2004).
   PubMed Web of Science ®Google Scholar
• Hegardt P, Widegren B, Sjogren HO. Nitric-oxide-dependent systemic immunosuppression in animals with progressively growing malignant gliomas. Cell Immunol.200(2), 116–127 (2000).
   PubMed Web of Science ®Google Scholar
• Di Tomaso T, Mazzoleni S, Wang E et al. Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clin. Cancer Res.16(3), 800–813 (2010).
   PubMed Web of Science ®Google Scholar
• Weller M, Frei K, Groscurth P, Krammer PH, Yonekawa Y, Fontana A. Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines. J. Clin. Invest.94(3), 954–964 (1994).
   PubMed Web of Science ®Google Scholar
• Saas P, Walker PR, Hahne M et al. Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain? J. Clin. Invest.99(6), 1173–1178 (1997).
   PubMed Web of Science ®Google Scholar
• Shinohara H, Yagita H, Ikawa Y, Oyaizu N. Fas drives cell cycle progression in glioma cells via extracellular signal-regulated kinase activation. Cancer Res.60(6), 1766–1772 (2000).
   PubMed Web of Science ®Google Scholar
• Fujii M, Ishii Y, Wakabayashi T et al. Cytologic diagnosis of male breast cancer with nipple discharge. A case report. Acta Cytol.30(1), 21–24 (1986).
   Google Scholar
• Kojima S, Sekine H, Fukui I, Ohshima H. Clinical significance of ‘cannibalism’ in urinary cytology of bladder cancer. Acta Cytol.42(6), 1365–1369 (1998).
   PubMed Web of Science ®Google Scholar
• Kumar PV, Hosseinzadeh M, Bedayat GR. Cytologic findings of medulloblastoma in crush smears. Acta Cytol.45(4), 542–546 (2001).
   Google Scholar
• Desimone PA, East R, Powell RD, Jr. Phagocytic tumor cell activity in oat cell carcinoma of the lung. Hum. Pathol.11(5 Suppl.), 535–539 (1980).
   PubMed Web of Science ®Google Scholar
• Caruso RA, Muda AO, Bersiga A, Rigoli L, Inferrera C. Morphological evidence of neutrophil–tumor cell phagocytosis (cannibalism) in human gastric adenocarcinomas. Ultrastruct. Pathol.26(5), 315–321 (2002).
   PubMed Web of Science ®Google Scholar
• Lugini L, Lozupone F, Matarrese P et al. Potent phagocytic activity discriminates metastatic and primary human malignant melanomas: a key role of ezrin. Lab. Invest.83(11), 1555–1567 (2003).
   PubMed Web of Science ®Google Scholar
• Lugini L, Matarrese P, Tinari A et al. Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells. Cancer Res.66(7), 3629–3638 (2006).
   PubMed Web of Science ®Google Scholar
• Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, Ley TJ. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity21(4), 589–601 (2004).
   PubMed Web of Science ®Google Scholar
• Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat. Rev. Cancer5(4), 263–274 (2005).
   PubMed Web of Science ®Google Scholar
• Gondek DC, Lu LF, Quezada SA, Sakaguchi S, Noelle RJ. Cutting edge: contact-mediated suppression by CD4+ CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J. Immunol.174(4), 1783–1786 (2005).
   PubMed Web of Science ®Google Scholar
• Chaput N, Darrasse-Jeze G, Bergot AS et al. Regulatory T cells prevent CD8 T cell maturation by inhibiting CD4 Th cells at tumor sites. J. Immunol.179(8), 4969–4978 (2007).
   PubMed Web of Science ®Google Scholar
• Mizukami Y, Kono K, Kawaguchi Y et al. CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer. Int. J. Cancer122(10), 2286–2293 (2008).
   PubMed Web of Science ®Google Scholar
• Curiel TJ, Coukos G, Zou L et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med.10(9), 942–949 (2004).
   PubMed Web of Science ®Google Scholar
• El Andaloussi A, Han Y, Lesniak MS. Prolongation of survival following depletion of CD4+ CD25+ regulatory T cells in mice with experimental brain tumors. J. Neurosurg.105(3), 430–437 (2006).
   PubMed Web of Science ®Google Scholar
• 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. Cancer121(1), 95–105 (2007).
   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 Oncol.8(3), 234–243 (2006).
   PubMed Web of Science ®Google Scholar
• El Andaloussi A, Lesniak MS. CD4+ CD25+ FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas. J. Neurooncol.83(2), 145–152 (2007).
   PubMed Web of Science ®Google Scholar
• Pellegatta S, Poliani PL, Stucchi E et al. Intra-tumoral dendritic cells increase efficacy of peripheral vaccination by modulation of glioma microenvironment. Neuro Oncol.12(4), 377–388 (2010).
   Google Scholar
• Liyanage UK, Moore TT, Joo HG et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J. Immunol.169(5), 2756–2761 (2002).
   PubMed Web of Science ®Google Scholar
• Somasundaram R, Jacob L, Swoboda R et al. Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta. Cancer Res.62(18), 5267–5272 (2002).
   PubMed Web of Science ®Google Scholar
• Ichihara F, Kono K, Takahashi A, Kawaida H, Sugai H, Fujii H. Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers. Clin. Cancer Res.9(12), 4404–4408 (2003).
   PubMed Web of Science ®Google Scholar
• Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A. CD4+ CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer98(5), 1089–1099 (2003).
   PubMed Web of Science ®Google Scholar
• Karube K, Ohshima K, Tsuchiya T et al. Expression of FoxP3, a key molecule in CD4CD25 regulatory T cells, in adult T-cell leukaemia/lymphoma cells. Br. J. Haematol.126(1), 81–84 (2004).
   PubMed Web of Science ®Google Scholar
• Woo EY, Chu CS, Goletz TJ et al. Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res.61(12), 4766–4772 (2001).
   PubMed Web of Science ®Google Scholar
• Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin. Cancer Res.9(2), 606–612 (2003).
   PubMed Web of Science ®Google Scholar
• Marshall NA, Christie LE, Munro LR et al. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood103(5), 1755–1762 (2004).
   PubMed Web of Science ®Google Scholar
• Viguier M, Lemaitre F, Verola O et al. Foxp3 expressing CD4+ CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J. Immunol.173(2), 1444–1453 (2004).
   PubMed Web of Science ®Google Scholar
• Gray CP, Arosio P, Hersey P. Association of increased levels of heavy-chain ferritin with increased CD4+ CD25+ regulatory T-cell levels in patients with melanoma. Clin. Cancer Res.9(7), 2551–2559 (2003).
   PubMed Web of Science ®Google Scholar
• Jacobs JF, Idema AJ, Bol KF et al. Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors. Neuro Oncol.11(4), 394–402 (2009).
   PubMed Web of Science ®Google Scholar
• Colombo MP, Piconese S. Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat. Rev. Cancer7(11), 880–887 (2007).
   PubMed Web of Science ®Google Scholar
• Whiteside TL. Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunol. Immunother.48(7), 346–352 (1999).
   PubMed Web of Science ®Google Scholar
• Dworacki G, Meidenbauer N, Kuss I et al. Decreased zeta chain expression and apoptosis in CD3+ peripheral blood T lymphocytes of patients with melanoma. Clin. Cancer Res.7(3 Suppl.), 947s–957s (2001).
   PubMed Web of Science ®Google Scholar
• Reichert TE, Strauss L, Wagner EM, Gooding W, Whiteside TL. Signaling abnormalities, apoptosis, and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin. Cancer Res.8(10), 3137–3145 (2002).
   PubMed Web of Science ®Google Scholar
• Whiteside TL. Down-regulation of ζ-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol. Immunother.53(10), 865–878 (2004).
   PubMed Web of Science ®Google Scholar
• Dix AR, Brooks WH, Roszman TL, Morford LA. Immune defects observed in patients with primary malignant brain tumors. J. Neuroimmunol.100(1–2), 216–232 (1999).
   PubMed Web of Science ®Google Scholar
• Soderberg A, Barral AM, Soderstrom M, Sander B, Rosen A. Redox-signaling transmitted in trans to neighboring cells by melanoma-derived TNF-containing exosomes. Free Radic. Biol. Med.43(1), 90–99 (2007).
   PubMed Web of Science ®Google Scholar
• Clayton A, Mitchell JP, Court J, Mason MD, Tabi Z. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res.67(15), 7458–7466 (2007).
   PubMed Web of Science ®Google Scholar
• Andreola G, Rivoltini L, Castelli C et al. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J. Exp. Med.195(10), 1303–1316 (2002).
   PubMed Web of Science ®Google Scholar
• Safaei R, Larson BJ, Cheng TC et al. Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol. Cancer Ther.4(10), 1595–1604 (2005).
   PubMed Web of Science ®Google Scholar
• Luciani F, Spada M, De Milito A et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J. Natl Cancer Inst.96(22), 1702–1713 (2004).
   PubMed Web of Science ®Google Scholar
• Graner MW, Cumming RI, Bigner DD. The heat shock response and chaperones/heat shock proteins in brain tumors: surface expression, release, and possible immune consequences. J. Neurosci.27(42), 11214–11227 (2007).
   PubMed Web of Science ®Google Scholar
• Skog J, Wurdinger T, Van Rijn S et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol.10(12), 1470–1476 (2008).
   PubMed Web of Science ®Google Scholar
• Al-Nedawi K, Meehan B, Micallef J et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol.10(5), 619–624 (2008).
   PubMed Web of Science ®Google Scholar
• Graner MW, Alzate O, Dechkovskaia AM et al. Proteomic and immunologic analyses of brain tumor exosomes. FASEB J.23(5), 1541–1557 (2009).
   PubMed Web of Science ®Google Scholar
• Stupp R, Mason WP, Van Den Bent MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med.352(10), 987–996 (2005).
   PubMed Web of Science ®Google Scholar
• Stupp R, Hegi ME, Mason WP 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.10(5), 459–466 (2009).
   PubMed Web of Science ®Google Scholar
• Park DM, Sathornsumetee S, Rich JN. Medical oncology: treatment and management of malignant gliomas. Nat. Rev. Clin. Oncol.7(2), 75–77 (2010).
   Google Scholar
• Gilboa E. DC-based cancer vaccines. J. Clin. Invest.117(5), 1195–1203 (2007).
   PubMed Web of Science ®Google Scholar
• De Vleeschouwer S, Fieuws S, Rutkowski S et al. Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme. Clin. Cancer Res.14(10), 3098–3104 (2008).
   PubMed Web of Science ®Google Scholar
• Kikuchi T, Akasaki Y, Irie M, Homma S, Abe T, Ohno T. Results of a Phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells. Cancer Immunol. Immunother.50(7), 337–344 (2001).
   PubMed Web of Science ®Google Scholar
• Kikuchi T, Akasaki Y, Abe T et al. Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12. J. Immunother.27(6), 452–459 (2004).
   PubMed Web of Science ®Google Scholar
• Liau LM, Prins RM, Kiertscher SM et al. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin. Cancer Res.11(15), 5515–5525 (2005).
   PubMed Web of Science ®Google Scholar
• Rutkowski S, De Vleeschouwer S, Kaempgen E et al. Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study. Br. J. Cancer91(9), 1656–1662 (2004).
   PubMed Web of Science ®Google Scholar
• Wheeler CJ, Black KL, Liu G et al. Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res.68(14), 5955–5964 (2008).
   PubMed Web of Science ®Google Scholar
• Yamanaka R, Abe T, Yajima N et al. Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical Phase I/II trial. Br. J. Cancer89(7), 1172–1179 (2003).
   PubMed Web of Science ®Google Scholar
• Yamanaka R, Homma J, Yajima N et al. Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical Phase I/II trial. Clin. Cancer Res.11(11), 4160–4167 (2005).
   PubMed Web of Science ®Google Scholar
• Yu JS, Wheeler CJ, Zeltzer PM et al. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res.61(3), 842–847 (2001).
   PubMed Web of Science ®Google Scholar
• Yu JS, Liu G, Ying H, Yong WH, Black KL, Wheeler CJ. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res.64(14), 4973–4979 (2004).
   PubMed Web of Science ®Google Scholar
• De Vries IJ, Lesterhuis WJ, Scharenborg NM et al. Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. Clin. Cancer Res.9(14), 5091–5100 (2003).
   PubMed Web of Science ®Google Scholar
• De Vries IJ, Krooshoop DJ, Scharenborg NM et al. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res.63(1), 12–17 (2003).
   PubMed Web of Science ®Google Scholar
• Jonuleit H, Kuhn U, Muller G et al. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol.27(12), 3135–3142 (1997).
   PubMed Web of Science ®Google Scholar
• Grauer OM, Sutmuller RP, Van Maren W et al. Elimination of regulatory T cells is essential for an effective vaccination with tumor lysate-pulsed dendritic cells in a murine glioma model. Int. J. Cancer122(8), 1794–1802 (2008).
   PubMed Web of Science ®Google Scholar
• Mitchell DA, Cui X, Schmittling RJ et al. Monoclonal antibody blockade of IL-2 receptor {alpha} during lymphopenia selectively depletes regulatory T cells in mice and humans. Blood118(11), 3003–3012 (2011).
   PubMed Web of Science ®Google Scholar
• Jacobs JF, Idema AJ, Bol KF et al. Prognostic significance and mechanism of Treg infiltration in human brain tumors. J. Neuroimmunol.225(1–2), 195–199 (2010).
   PubMed Web of Science ®Google Scholar
• Redjal N, Chan JA, Segal RA, Kung AL. CXCR4 inhibition synergizes with cytotoxic chemotherapy in gliomas. Clin. Cancer Res.12(22), 6765–6771 (2006).
   PubMed Web of Science ®Google Scholar
• Banissi C, Ghiringhelli F, Chen L, Carpentier AF. Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model. Cancer Immunol. Immunother.58(10), 1627–1634 (2009).
   PubMed Web of Science ®Google Scholar
• 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.57(1), 123–131 (2008).
   PubMed Web of Science ®Google Scholar
• Apetoh L, Ghiringhelli F, Tesniere A et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med.13(9), 1050–1059 (2007).
   PubMed Web of Science ®Google Scholar
• Haynes NM, Van Der Most RG, Lake RA, Smyth MJ. Immunogenic anti-cancer chemotherapy as an emerging concept. Curr. Opin. Immunol.20(5), 545–557 (2008).
   PubMed Web of Science ®Google Scholar
• Wheeler CJ, Das A, Liu G, Yu JS, Black KL. Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin. Cancer Res.10(16), 5316–5326 (2004).
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Sun W, Hussain SF et al. Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: case study. Neuro Oncol.10(1), 98–103 (2008).
   PubMed Web of Science ®Google Scholar
• Dhodapkar MV. Immunity to stemness genes in human cancer. Curr. Opin. Immunol.22(2), 245–250 (2010).
   PubMedGoogle Scholar
• Schmitz M, Temme A, Senner V et al. Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy. Br. J. Cancer96(8), 1293–1301 (2007).
   PubMed Web of Science ®Google Scholar
• Ueda R, Ohkusu-Tsukada K, Fusaki N et al. Identification of HLA-A2- and A24-restricted T-cell epitopes derived from SOX6 expressed in glioma stem cells for immunotherapy. Int. J. Cancer126(4), 919–929 (2010).
   PubMed Web of Science ®Google Scholar
• Parsons DW, Jones S, Zhang X et al. An integrated genomic analysis of human glioblastoma multiforme. Science321(5897), 1807–1812 (2008).
   PubMed Web of Science ®Google Scholar
• Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature455(7216), 1061–1068 (2008).
   PubMed Web of Science ®Google Scholar
• Verhaak RG, Hoadley KA, Purdom E et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell17(1), 98–110 (2010).
   PubMed Web of Science ®Google Scholar
• Prins RM, Soto H, Konkankit V et al. Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin. Cancer Res.17(6), 1603–1615 (2011).
   PubMed Web of Science ®Google Scholar
• Gan HK, Kaye AH, Luwor RB. The EGFRvIII variant in glioblastoma multiforme. J. Clin. Neurosci.16(6), 748–754 (2009).
   PubMed Web of Science ®Google Scholar
• Sahin O, Wiemann S. Functional genomics and proteomics approaches to study the ERBB network in cancer. FEBS Lett.583(11), 1766–1771 (2009).
   Google Scholar
• Omuro AM. What is the relevance of determining EGFR-variant-III status in glioblastomas? Nat. Clin. Pract. Oncol.5(4), 188–189 (2008).
   PubMedGoogle Scholar
• Shinojima N, Tada K, Shiraishi S et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res.63(20), 6962–6970 (2003).
   PubMed Web of Science ®Google Scholar
• Pelloski CE, Ballman KV, Furth AF et al. Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J. Clin. Oncol.25(16), 2288–2294 (2007).
   PubMed Web of Science ®Google Scholar
• Inda MM, Bonavia R, Mukasa A et al. Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma. Genes Dev.24(16), 1731–1745 (2010).
   PubMed Web of Science ®Google Scholar
• Nishikawa R, Ji XD, Harmon RC et al. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc. Natl Acad. Sci. USA91(16), 7727–7731 (1994).
   PubMed Web of Science ®Google Scholar
• Huang PH, Mukasa A, Bonavia R et al. Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma. Proc. Natl Acad. Sci. USA104(31), 12867–12872 (2007).
   PubMed Web of Science ®Google Scholar
• Horvath S, Zhang B, Carlson M et al. Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target. Proc. Natl Acad. Sci. USA103(46), 17402–17407 (2006).
   PubMed Web of Science ®Google Scholar
• Mishima K, Johns TG, Luwor RB et al. Growth suppression of intracranial xenografted glioblastomas overexpressing mutant epidermal growth factor receptors by systemic administration of monoclonal antibody (mAb) 806, a novel monoclonal antibody directed to the receptor. Cancer Res.61(14), 5349–5354 (2001).
   PubMed Web of Science ®Google Scholar
• Lal A, Glazer CA, Martinson HM et al. Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion. Cancer Res.62(12), 3335–3339 (2002).
   PubMed Web of Science ®Google Scholar
• Magnus N, Garnier D, Rak J. Oncogenic epidermal growth factor receptor up-regulates multiple elements of the tissue factor signaling pathway in human glioma cells. Blood116(5), 815–818 (2010).
   PubMed Web of Science ®Google Scholar
• Choi BD, Archer GE, Mitchell DA et al. EGFRvIII-targeted vaccination therapy of malignant glioma. Brain Pathol.19(4), 713–723 (2009).
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Archer GE, Crotty LE et al. Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma. Neurosurgery50(1), 158–164; discussion 164–165 (2002).
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Crotty LE, Archer GE et al. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin. Cancer Res.9(11), 4247–4254 (2003).
   PubMed Web of Science ®Google Scholar
• Sampson JH, Archer GE, Mitchell DA et al. An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol. Cancer Ther.8(10), 2773–2779 (2009).
   PubMed Web of Science ®Google Scholar
• Sampson JH, Heimberger AB, Archer GE et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J. Clin. Oncol.28(31), 4722–4729 (2010).
   PubMed Web of Science ®Google Scholar
• Bredel M, Scholtens DM, Yadav AK et al.NFKBIA deletion in glioblastomas. N. Engl. J. Med.364(7), 627–637 (2010).
   Google Scholar
• Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB, Rich JN. Hypoxia inducible factors in cancer stem cells. Br. J. Cancer102(5), 789–795 (2010).
   PubMed Web of Science ®Google Scholar
• Vredenburgh JJ, Desjardins A, Herndon JE, 2nd et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin. Cancer Res.13(4), 1253–1259 (2007).
   PubMed Web of Science ®Google Scholar
• Vredenburgh JJ, Desjardins A, Herndon JE, 2nd et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J. Clin. Oncol.25(30), 4722–4729 (2007).
   PubMed Web of Science ®Google Scholar
• Friedman HS, Prados MD, Wen PY et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J. Clin. Oncol.27(28), 4733–4740 (2009).
   PubMed Web of Science ®Google Scholar
• Lucio-Eterovic AK, Piao Y, De Groot JF. Mediators of glioblastoma resistance and invasion during antivascular endothelial growth factor therapy. Clin. Cancer Res.15(14), 4589–4599 (2009).
   PubMed Web of Science ®Google Scholar
• Gabrilovich D, Ishida T, Oyama T et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood92(11), 4150–4166 (1998).
   PubMed Web of Science ®Google Scholar
• Oyama T, Ran S, Ishida T et al. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J. Immunol.160(3), 1224–1232 (1998).
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI, Chen HL, Girgis KR et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat. Med.2(10), 1096–1103 (1996).
   PubMed Web of Science ®Google Scholar
• Ohm JE, Gabrilovich DI, Sempowski GD et al. VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood101(12), 4878–4886 (2003).
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Sampson JH. Immunotherapy coming of age: what will it take to make it standard of care for glioblastoma? Neuro Oncol.13(1), 3–13 (2010).
   Google Scholar
• Bogdahn U, Hau P, Stockhammer G et al. Targeted therapy for high-grade glioma with the TGF-{beta}2 inhibitor trabedersen: results of a randomized and controlled Phase IIb study. Neuro Oncol.13(1), 132–142 (2011).
   PubMed Web of Science ®Google Scholar
• Anido J, Saez-Borderias A, Gonzalez-Junca A et al. TGF-beta receptor inhibitors target the CD44(high)/Id1(high) glioma-Initiating cell population in human glioblastoma. Cancer Cell18(6), 655–668 (2010).
   PubMed Web of Science ®Google Scholar
• Pellegatta S, Poliani PL, Corno D et al. Neurospheres enriched in cancer stem–like cells are highly effective in eliciting a dendritic cell–mediated immune response against malignant gliomas. Cancer Res.earch66(21), 10247–10252 (2006).
   PubMed Web of Science ®Google Scholar
• Kalinski P, Mailliard RB, Giermasz A et al. Natural killer-dendritic cell cross-talk in cancer immunotherapy. Expert Opin. Biol. Ther.5(10), 1303–1315 (2005).
   PubMed Web of Science ®Google Scholar
• Burke S, Lakshmikanth T, Colucci F, Carbone E. New views on natural killer cell-based immunotherapy for melanoma treatment. Trends Immunol.31(9), 339–345 (2010).
   Google Scholar
• Cho D, Shook DR, Shimasaki N, Chang YH, Fujisaki H, Campana D. Cytotoxicity of activated natural killer cells against pediatric solid tumors. Clin. Cancer Res.16(15), 3901–3909 (2010).
   PubMed Web of Science ®Google Scholar
• Xu H, Cheung IY, Guo HF, Cheung NK. MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. Cancer Res.69(15), 6275–6281 (2009).
   PubMed Web of Science ®Google Scholar
• Ueda R, Kohanbash G, Sasaki K et al. Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc. Natl Acad. Sci. USA106(26), 10746–10751 (2009).
   PubMed Web of Science ®Google Scholar
• Grauer OM, Molling JW, Bennink E et al. TLR ligands in the local treatment of established intracerebral murine gliomas. J. Immunol.181(10), 6720–6729 (2008).
   PubMed Web of Science ®Google Scholar
• Korman AJ, Peggs KS, Allison JP. Checkpoint blockade in cancer immunotherapy. Adv. Immunol.90, 297–339 (2006).
   PubMed Web of Science ®Google Scholar
• Hodi FS, O’day SJ, Mcdermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med.363(8), 711–723 (2010).
   PubMed Web of Science ®Google Scholar
• 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.13(7), 2158–2167 (2007).
   PubMed Web of Science ®Google Scholar
• Engelhardt B. Molecular mechanisms involved in T cell migration across the blood–brain barrier. J. Neural Transm.113(4), 477–485 (2006).
   PubMed Web of Science ®Google Scholar