The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy

被引:182
作者
Smits, Evelien L. J. M. [1 ]
Ponsaerts, Peter [1 ]
Berneman, Zwi N. [1 ,2 ]
Van Tendeloo, Viggo F. I. [1 ,2 ]
机构
[1] Univ Antwerp, VIDI, Lab Expt Hematol, Fac Med, B-2650 Antwerp, Belgium
[2] Univ Antwerp Hosp, Ctr Cellular Therapy & Regenerat Med, Antwerp, Belgium
关键词
TLR7; TLR8; TLR ligands; cancer; immunotherapy; vaccine adjuvant;
D O I
10.1634/theoncologist.2008-0097
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The importance of Toll-like receptors (TLRs) in stimulating innate and adaptive immunity is now well established. In view of this, TLR ligands have become interesting targets to use as stand-alone immunotherapeutics or vaccine adjuvants for cancer treatment. TLR7 and TLR8 were found to be closely related, sharing their intracellular endosomal location, as well as their ligands. In this review, we describe the agonists of TLR7 and TLR8 that are known so far, as well as their contribution to antitumor responses by affecting immune cells, tumor cells, and the tumor microenvironment. The major benefit of TLR7/8 agonists as immune response enhancers is their simultaneous stimulation of several cell types, resulting in a mix of activated immune cells, cytokines and chemokines at the tumor site. We discuss the studies that used TLR7/8 agonists as stand-alone immunotherapeutics or cancer vaccine adjuvants, as well as the potential of TLR7/8 ligands to enhance antitumor responses in passive immunotherapy approaches.
引用
收藏
页码:859 / 875
页数:17
相关论文
共 164 条
[61]   Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo [J].
Judge, AD ;
Bola, G ;
Lee, ACH ;
MacLachlan, I .
MOLECULAR THERAPY, 2006, 13 (03) :494-505
[62]   Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848 [J].
Jurk, M ;
Heil, F ;
Vollmer, J ;
Schetter, C ;
Krieg, AM ;
Wagner, H ;
Lipford, G ;
Bauer, S .
NATURE IMMUNOLOGY, 2002, 3 (06) :499-499
[63]   Modulating responsiveness of human TLR7 and 8 to small molecule ligands with T-rich phosphorothiate oligodeoxynucleotides [J].
Jurk, Marion ;
Kritzler, Andrea ;
Schulte, Bettina ;
Tluk, Sibylle ;
Schetter, Christian ;
Krieg, Arthur M. ;
Vollmer, Joerg .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2006, 36 (07) :1815-1826
[64]   Suppression of RNA recognition by Toll-like receptors:: The impact of nucleoside modification and the evolutionary origin of RNA [J].
Karikó, K ;
Buckstein, M ;
Ni, HP ;
Weissman, D .
IMMUNITY, 2005, 23 (02) :165-175
[65]   TLR signaling [J].
Kawai, Taro ;
Akira, Shizuo .
SEMINARS IN IMMUNOLOGY, 2007, 19 (01) :24-32
[66]   Matrix metalloproteinases in tumor progression:: focus on basal and squamous cell skin cancer [J].
Kerkelä, E ;
Saarialho-Kere, U .
EXPERIMENTAL DERMATOLOGY, 2003, 12 (02) :109-125
[67]  
KONO T, 1994, LYMPHOKINE CYTOK RES, V13, P71
[68]   Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis - Results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials [J].
Korman, N ;
Moy, R ;
Ling, M ;
Matheson, R ;
Smith, S ;
McKane, S ;
Lee, JH .
ARCHIVES OF DERMATOLOGY, 2005, 141 (04) :467-473
[69]   Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity [J].
Krieg, Arthur M. ;
Vollmer, Joerg .
IMMUNOLOGICAL REVIEWS, 2007, 220 :251-269
[70]   Combined Toll-like receptor agonists synergistically increase production of inflammatory cytokines in human neonatal dendritic cells [J].
Krumbiegel, Doreen ;
Zepp, Fred ;
Meyer, Claudius Ullrich .
HUMAN IMMUNOLOGY, 2007, 68 (10) :813-822