Abstract
Immunotherapy strategies targeting glioma stem-like cells (GSCs) hold promise for improving outcomes in glioblastoma patients. We used the A2B5 monoclonal antibody to classify GSCs derived from the mouse GL261 glioma cell line, and A2B5+ GL261 cell lysate-pulsed dendritic cells (DCs) were used to treat mouse glioma. We found that such DCs elicited a stronger specific cytotoxic T lymphocyte response against A2B5+ GL261 cells than A2B5– GL261 cell lysate-pulsed DCs. The effect of A2B5+ GL261 cell lysate-pulsed DCs in vivo depended on when the vaccination was started. In the tumor cell adaptation phase, C57BL/6 mice had an immune response against GL261, and vaccination enhanced the immune response and prevented glioma formation in 37.5 % of mice. In contrast, after glioma formation, the immune response against GL261 was decreased, and vaccination had no therapeutic effect. Our findings suggest that vaccination with A2B5+ GL261 cell lysate-pulsed DCs only has some glioma preventive effect.
Similar content being viewed by others
References
Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021. doi:10.1158/0008-5472.CAN-04-1364
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401. doi:10.1038/nature03128
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760. doi:10.1038/nature05236
Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67. doi:10.1186/1476-4598-5-67
Hatiboglu MA, Wei J, Wu AS, Heimberger AB (2010) Immune therapeutic targeting of glioma cancer stem cells. Target Oncol 5:217–227. doi:10.1007/s11523-010-0151-8
Pellegatta S, Poliani PL, Corno D, Menghi F, Ghielmetti F, Suarez-Merino B, Caldera V, Nava S, Ravanini M, Facchetti F, Bruzzone MG, Finocchiaro G (2006) Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas. Cancer Res 66:10247–10252. doi:10.1158/0008-5472.CAN-06-2048
Woolard K, Fine HA (2009) Glioma stem cells: better flat than round. Cell Stem Cell 4:466–467. doi:10.1016/j.stem.2009.05.013
Ogden AT, Waziri AE, Lochhead RA, Fusco D, Lopez K, Ellis JA, Kang J, Assanah M, McKhann GM, Sisti MB, McCormick PC, Canoll P, Bruce JN (2008) Identification of A2B5+ CD133− tumor-initiating cells in adult human gliomas. Neurosurgery 62:505–514. doi:10.1227/01.neu.0000316019.28421.95
Tchoghandjian A, Baeza N, Colin C, Cayre M, Metellus P, Beclin C, Ouafik L, Figarella-Branger D (2010) A2B5 cells from human glioblastoma have cancer stem cell properties. Brain Pathol 20:211–221. doi:10.1111/j.1750-3639.2009.00269.x
Son MJ, Woolard K, Nam DH, Lee J, Fine HA (2009) SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell 4:440–452. doi:10.1016/j.stem.2009.03.003
Wu A, Oh S, Wiesner SM, Ericson K, Chen L, Hall WA, Champoux PE, Low WC, Ohlfest JR (2008) Persistence of CD133+ cells in human and mouse glioma cell lines: detailed characterization of GL261 glioma cells with cancer stem cell-like properties. Stem Cells Dev 17:173–184. doi:10.1089/scd.2007.0133
Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, Aigner L, Brawanski A, Bogdahn U, Beier CP (2007) CD133(+) and CD133(−) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 67:4010–4015. doi:10.1158/0008-5472.CAN-06-4180
Jedema I, van der Werff NM, Barge RM, Willemze R, Falkenburg JH (2004) New CFSE-based assay to determine susceptibility to lysis by cytotoxic T cells of leukemic precursor cells within a heterogeneous target cell population. Blood 103:2677–2682. doi:10.1182/blood-2003-06-2070
Prins RM, Odesa SK, Liau LM (2003) Immunotherapeutic targeting of shared melanoma-associated antigens in a murine glioma model. Cancer Res 63:8487–8491
Biollaz G, Bernasconi L, Cretton C, Püntener U, Frei K, Fontana A, Suter T (2009) Site-specific anti-tumor immunity: differences in DC function, TGF-beta production and numbers of intratumoral Foxp3+ Treg. Eur J Immunol 39:1323–1333. doi:10.1002/eji.200838921
Maes W, Deroose C, Reumers V, Krylyshkina O, Gijsbers R, Baekelandt V, Ceuppens J, Debyser Z, Van Gool SW (2009) In vivo bioluminescence imaging in an experimental mouse model for dendritic cell based immunotherapy against malignant glioma. J Neurooncol 91:127–139. doi:10.1007/s11060-008-9691-5
Maes W, Van Gool SW (2011) Experimental immunotherapy for malignant glioma: lessons from two decades of research in the GL261 model. Cancer Immunol Immunother 60:153–160. doi:10.1007/s00262-010-0946-6
Newcomb EW, Zagzag D (2009) The murine GL261 glioma experimental model to access novel brain tumor treatments. In: Van Meir EG (ed) CNS cancer: models, markers, prognostic factors, targets, and therapeutic approaches. Humana Press (Springer), New York, pp 227–241. doi:10.1007/978-1-60327-553-8
Szatmári T, Lumniczky K, Désaknai S, Trajcevski S, Hídvégi EJ, Hamada H, Sáfrány G (2006) Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy. Cancer Sci 97:546–553. doi:10.1111/j.1349-7006.2006.00208.x
Ksendzovsky A, Feinstein D, Zengou R, Sharp A, Polak P, Lichtor T, Glick RP (2009) Investigation of immunosuppressive mechanisms in a mouse glioma model. J Neurooncol 93:107–114. doi:10.1007/s11060-009-9884-6
Wei J, Barr J, Kong LY, Wang Y, Wu A, Sharma AK, Gumin J, Henry V, Colman H, Sawaya R, Lang FF, Heimberger AB (2010) Glioma-associated cancer-initiating cells induce immunosuppression. Clin Cancer Res 16:461–473. doi:10.1158/1078-0432.CCR-09-1983
Di Tomaso T, Mazzoleni S, Wang E, Sovena G, Clavenna D, Franzin A, Mortini P, Ferrone S, Doglioni C, Marincola FM, Galli R, Parmiani G, Maccalli C (2010) Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clin Cancer Res 16:800–813. doi:10.1158/1078-0432.CCR-09-2730
Brown CE, Starr R, Martinez C, Aguilar B, D’Apuzzo M, Todorov I, Shih CC, Badie B, Hudecek M, Riddell SR, Jensen MC (2009) Recognition and killing of brain tumor stem-like initiating cells by CD8+ cytolytic T cells. Cancer Res 69:8886–8893. doi:10.1158/0008-5472.CAN-09-2687
Hua W, Yao Y, Chu Y, Zhong P, Sheng X, Xiao B, Wu J, Yang B, Mao Y, Zhou L (2011) The CD133+ tumor stem-like cell-associated antigen may elicit highly intense immune responses against human malignant glioma. J Neurooncol 105:149–157. doi:10.1007/s11060-011-0572-y
Xu Q, Liu G, Yuan X, Xu M, Wang H, Ji J, Konda B, Black KL, Yu JS (2009) Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens. Stem cells 27:1734–1740. doi:10.1002/stem.102
Grauer OM, Sutmuller RP, van Maren W, Jacobs JF, Bennink E, Toonen LW, Nierkens S, Adema GJ (2008) Elimination of regulatory T cells is essential for an effective vaccination with tumor lysate-pulsed dendritic cells in a murine glioma model. Int J Cancer 122:1794–1802. doi:10.1002/ijc.23284
Finn OJ (2008) Cancer immunology. N Engl J Med 358:2704–2715. doi:10.1056/NEJMra072739
Ueda R, Fujita M, Zhu X, Sasaki K, Kastenhuber ER, Kohanbash G, McDonald HA, Harper J, Lonning S, Okada H (2009) Systemic inhibition of transforming growth factor-beta in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Clin Cancer Res 15:6551–6559. doi:10.1158/1078-0432.CCR-09-1067
Acknowledgments
This study was supported by the China National Natural Science Foundation (81001115 to W.H. and 81272797 to Y.Y.) and the Project for Science and Technology Commission of Shanghai Municipality Grant (No. 10JC1402200 to L.F.Z.).
Conflict of interest
None of the authors has any conflict of interest associated with the present work.
Author information
Authors and Affiliations
Corresponding author
Additional information
Ming Xu and Yu Yao contributed equally to this study.
Rights and permissions
About this article
Cite this article
Xu, M., Yao, Y., Hua, W. et al. Mouse glioma immunotherapy mediated by A2B5+ GL261 cell lysate-pulsed dendritic cells. J Neurooncol 116, 497–504 (2014). https://doi.org/10.1007/s11060-013-1334-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-013-1334-9