Immunomodulating role of bisphosphonates on human gamma delta T cells: an intriguing and promising aspect of their antitumour activity

被引:21
作者
Galluzzo, S. [1 ]
Santini, D. [1 ]
Vincenzi, B. [1 ]
Caccamo, N. [1 ]
Meraviglia, S. [1 ]
Salerno, A. [1 ]
Dieli, F. [1 ]
Tonini, G. [1 ]
机构
[1] Univ Campus Bio Med, I-00155 Rome, Italy
关键词
antitumour; bisphophonate; human gamma delta T cells; immunomodulatory; immunotherapy;
D O I
10.1517/14728222.11.7.941
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
V gamma 9V delta 2 T cells have the ability to produce inflammatory cytokines involved in protective immunity against intracellular pathogens and tumours and to display strong cytolytic as well as bactericidal activities. This suggests a direct involvement of V gamma 9V delta 2 T lymphocytes in immune control of cancer and infections. These observations have recently aided development of novel immunotherapeutic approaches aimed at V gamma 9V delta 2 T cell activation. Nitrogen-containing bisphosphonates (N-BPs) play a crucial role in V gamma 9V delta 2 T lymphocyte activation and in the acquisition of effector functions. The preliminary results of these innovative strategies are encouraging. Moreover, compelling evidence in the literature supports the hypothesis that the antitumour effect of bisphosphonates is exerted through direct as well as indirect mechanisms. An additional and not yet well explored mechanism by which N-BPs may display antineoplastic effect is related to their immunomodulatory properties. It is fascinating that N-BPs influence the immune system in various but interrelated ways, being able to enhance the innate and to promote the adaptive immune responses. For all these reasons, V gamma 9V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic protocols based on N-BP administration. All these unexpected effects of N-BPs on the immune system have opened new and intriguing possibilities of therapeutic use for these drugs.
引用
收藏
页码:941 / 954
页数:14
相关论文
共 100 条
[21]   New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and -independent effects [J].
Denoyelle, C ;
Hong, L ;
Vannier, JP ;
Soria, J ;
Soria, C .
BRITISH JOURNAL OF CANCER, 2003, 88 (10) :1631-1640
[22]   Potentiation of antigen-stimulated Vγ9Vδ2 T cell cytokine production by immature dendritic cells (DC) and recpirocal effect on DC maturation [J].
Devilder, MC ;
Maillet, S ;
Bouyge-Moreau, I ;
Donnadieu, E ;
Bonneville, M ;
Scotet, E .
JOURNAL OF IMMUNOLOGY, 2006, 176 (03) :1386-1393
[23]   Induction of γδ T-lymphocyte effector functions by bisphosphonate zoledronic acid in cancer patients in vivo [J].
Dieli, F ;
Gebbia, N ;
Poccia, F ;
Caccamo, N ;
Montesano, C ;
Fulfaro, F ;
Arcara, C ;
Valerio, MR ;
Meraviglia, S ;
Di Sano, C ;
Sireci, G ;
Salemo, A .
BLOOD, 2003, 102 (06) :2310-2311
[24]   Differentiation of effector/memory Vδ2 T cells and migratory routes in lymph nodes or inflammatory sites [J].
Dieli, F ;
Poccia, F ;
Lipp, M ;
Sireci, G ;
Caccamo, N ;
Di Sano, C ;
Salerno, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (03) :391-397
[25]   Inhibition of protein prenylation by bisphosphonates causes sustained activation of Rac, Cdc42, and Rho GTPases [J].
Dunford, JE ;
Rogers, MJ ;
Ebetino, FH ;
Phipps, RJ ;
Coxon, FP .
JOURNAL OF BONE AND MINERAL RESEARCH, 2006, 21 (05) :684-694
[26]  
Dunford JE, 2001, J PHARMACOL EXP THER, V296, P235
[27]  
*FDA, 2002, EXPERT REV ANTICANC, V2, P137
[28]   In vitro effects of aminobisphosphonates on Vγ9Vδ2 T cell activation and differentiation [J].
Ferlazzo, V. ;
Sferrazza, C. ;
Caccamo, N. ;
Di Fede, G. ;
Di Lorenzo, G. ;
D'Asaro, M. ;
Meraviglia, S. ;
Dieli, F. ;
Rini, G. ;
Salerno, A. .
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 2006, 19 (02) :309-317
[29]  
FIORE F, 2007, BLOOD
[30]   GAMMA-DELTA-T-CELL CLONES AND NATURAL-KILLER-CELL CLONES MEDIATE DISTINCT PATTERNS OF NONMAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED CYTOLYSIS [J].
FISCH, P ;
MALKOVSKY, M ;
BRAAKMAN, E ;
STURM, E ;
BOLHUIS, RLH ;
PRIEVE, A ;
SOSMAN, JA ;
LAM, VA ;
SONDEL, PM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (05) :1567-1579