Recent advances in the role of toll-like receptors and TLR agonists in immunotherapy for human glioma

被引:55
作者
Deng, Shuanglin [1 ,2 ]
Zhu, Shan [1 ]
Qiao, Yuan [1 ]
Liu, Yong-Jun [3 ]
Chen, Wei [4 ,5 ]
Zhao, Gang [2 ]
Chen, Jingtao [1 ]
机构
[1] Jilin Univ, Hosp 1, Inst Translat Med, Changchun 130031, Peoples R China
[2] Jilin Univ, Hosp 1, Dept Neurosurg, Changchun 130031, Peoples R China
[3] MedImmune, Gaithersburg, MD 20878 USA
[4] Univ Minnesota, Sch Med, Dept Hematol Oncol, Minneapolis, MN 55455 USA
[5] Univ Minnesota, Sch Med, BMT Dept Pediat, Minneapolis, MN 55455 USA
关键词
glioma; toll-like receptor; agonist; central nervous system; immunotherapy; BLOOD-BRAIN-BARRIER; NF-KAPPA-B; DENDRITIC CELLS; T-CELLS; IMMUNE-RESPONSES; IN-VIVO; INFLAMMATORY RESPONSES; ADJUVANT TEMOZOLOMIDE; MONONUCLEAR-CELLS; CHOROID-PLEXUS;
D O I
10.1007/s13238-014-0112-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Gliomas are extremely aggressive brain tumors with a very poor prognosis. One of the more promising strategies for the treatment of human gliomas is targeted immunotherapy where antigens that are unique to the tumors are exploited to generate vaccines. The approach, however, is complicated by the fact that human gliomas escape immune surveillance by creating an immune suppressed microenvironment. In order to oppose the glioma imposed immune suppression, molecules and pathways involved in immune cell maturation, expansion, and migration are under intensive clinical investigation as adjuvant therapy. Toll-like receptors (TLRs) mediate many of these functions in immune cell types, and TLR agonists, thus, are currently primary candidate molecules to be used as important adjuvants in a variety of cancers. In animal models for glioma, TLR agonists have exhibited antitumor properties by facilitating antigen presentation and stimulating innate and adaptive immunity. In clinical trials, several TLR agonists have achieved survival benefit, and many more trials are recruiting or ongoing. However, a second complicating factor is that TLRs are also expressed on cancer cells where they can participate instead in a variety of tumor promoting activities including cell growth, proliferation, invasion, migration, and even stem cell maintenance. TLR agonists can, therefore, possibly play dual roles in tumor biology. Here, how TLRs and TLR agonists function in glioma biology and in anti-glioma therapies is summarized in an effort to provide a current picture of the sophisticated relationship of glioma with the immune system and the implications for immunotherapy.
引用
收藏
页码:899 / 911
页数:13
相关论文
共 106 条
[1]   Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant [J].
Adams, Sylvia ;
O'Neill, David W. ;
Nonaka, Daisuke ;
Hardin, Elizabeth ;
Chiriboga, Luis ;
Siu, Kimberly ;
Cruz, Crystal M. ;
Angiulli, Angelica ;
Angiulli, Francesca ;
Ritter, Erika ;
Holman, Rose Marie ;
Shapiro, Richard L. ;
Berman, Russell S. ;
Berner, Natalie ;
Shao, Yongzhao ;
Manches, Olivier ;
Pan, Linda ;
Venhaus, Ralph R. ;
Hoffman, Eric W. ;
Jungbluth, Achim ;
Gnjatic, Sacha ;
Old, Lloyd ;
Pavlick, Anna C. ;
Bhardwaj, Nina .
JOURNAL OF IMMUNOLOGY, 2008, 181 (01) :776-784
[2]   TLR1/2, TLR7, and TLR9 Signals Directly Activate Human Peripheral Blood Naive and Memory B Cell Subsets to Produce Cytokines, Chemokines, and Hematopoietic Growth Factors [J].
Agrawal, Sudhanshu ;
Gupta, Sudhir .
JOURNAL OF CLINICAL IMMUNOLOGY, 2011, 31 (01) :89-98
[3]   Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[4]   Inflammatory and anti-glioma effects of an adenovirus expressing human-soluble Fms-like tyrosine kinase 3 ligand (hsFIt3L): Treatment with hsFIt3L inhibits intracranial glioma progression [J].
Ali, S ;
Curtin, JF ;
Zirger, JM ;
Xiong, WD ;
King, GD ;
Barcia, C ;
Liu, CY ;
Puntel, M ;
Goverdhana, S ;
Lowenstein, PR ;
Castro, MG .
MOLECULAR THERAPY, 2004, 10 (06) :1071-1084
[5]   Induction of Anti-Glioma Natural Killer Cell Response following Multiple Low-Dose Intracerebral CpG Therapy [J].
Alizadeh, Darya ;
Zhang, Leying ;
Brown, Christine E. ;
Farrukh, Omar ;
Jensen, Michael C. ;
Badie, Behnam .
CLINICAL CANCER RESEARCH, 2010, 16 (13) :3399-3408
[6]   Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain [J].
Anandasabapathy, Niroshana ;
Victora, Gabriel D. ;
Meredith, Matthew ;
Feder, Rachel ;
Dong, Baojun ;
Kluger, Courtney ;
Yao, Kaihui ;
Dustin, Michael L. ;
Nussenzweig, Michel C. ;
Steinman, Ralph M. ;
Liu, Kang .
JOURNAL OF EXPERIMENTAL MEDICINE, 2011, 208 (08) :1695-1705
[7]   ESTABLISHMENT OF DORSAL-VENTRAL POLARITY IN THE DROSOPHILA EMBRYO - GENETIC-STUDIES ON THE ROLE OF THE TOLL GENE-PRODUCT [J].
ANDERSON, KV ;
JURGENS, G ;
NUSSLEINVOLHARD, C .
CELL, 1985, 42 (03) :779-789
[8]  
[Anonymous], JAK STAT
[9]   Toll-like receptor agonists induce apoptosis in mouse B-cell lymphoma cells by altering NF-κB activation [J].
Arunkumar, Nandini ;
Liu, Chaohong ;
Hang, Haiying ;
Song, Wenxia .
CELLULAR & MOLECULAR IMMUNOLOGY, 2013, 10 (04) :360-372
[10]   Novel signal transduction pathway utilized by extracellular HSP70 -: Role of Toll-like receptor (TLR) 2 AND TLR4 [J].
Asea, A ;
Rehli, M ;
Kabingu, E ;
Boch, JA ;
Baré, O ;
Auron, PE ;
Stevenson, MA ;
Calderwood, SK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (17) :15028-15034