PMID- 20549316
OWN - NLM
STAT- MEDLINE
DCOM- 20110315
LR  - 20211020
IS  - 1573-2592 (Electronic)
IS  - 0271-9142 (Linking)
VI  - 30
IP  - 5
DP  - 2010 Sep
TI  - Coculturing dendritic cells with zoledronate acid efficiently enhance the 
      anti-tumor effects of cytokine-induced killer cells.
PG  - 766-74
LID - 10.1007/s10875-010-9434-1 [doi]
AB  - INTRODUCTION: Dendritic cells (DCs) have greater stimulating activity on innate 
      and adaptive immunity following short-term sensitization with zoledronate acid 
      (DCs(Zol)). We identified the phenotype, cytotoxicity, and mechanisms of killing 
      of cytokine-induced killer (CIK) cells which were cocultured with DCs(Zol). 
      METHODS: Adherent and nonadherent cells of peripheral blood mononuclear cell from 
      myeloma patients were incubated for DCs and CIK cells. Then, the CIK cells were 
      cocultured with DCs(Zol) (DCs(Zol)-CIK). Expression of markers for DCs(Zol)-CIK 
      cells was measured using flow cytometry. Cytotoxicity was evaluated by against 
      human myeloma cell lines and mechanisms of killing were tested by selectively 
      blocking NKG2D receptor. The anti-tumor activity of these effector cells was 
      further evaluated using a nude mice tumor model. RESULTS: gammadelta TCR 
      expression of CIK cells significantly increased after coculture with immature or 
      mature DCs(Zol) (iDCs/mDCs(Zol)-CIK) and these cells aggressively lysed myeloma 
      cells compared with mDCs-CIK and zoledronate acid pulsed CIK cells (CIK(Zol); 
      50.8 +/- 7.9% and 48.2 +/- 4.7% versus 31.9 +/- 5.1% and 20.5 +/- 3.6%, effector 
      versus target ratio was 60:1). Both alphabeta T and gammadelta T cells in the 
      iDCs(Zol)-CIK cells performed the majority of lysis. The iDCs/mDCs(Zol)-CIK cells 
      greatly increased NKG2D expression compared with mDCs-CIK and CIK(Zol) during 
      culture (71.5 +/- 11.3% and 67.7 +/- 9.3% versus 51.3 +/- 6.2% and 
      47.1 +/- 5.7%). iDCs(Zol)-CIK cell-mediated lysis dropped 69.21% when the NKG2D 
      receptor was blocked and the cytotoxicity correlated with NKG2D ligand-MICA 
      expression on the target cells. In a human myeloma bearing nude mice model, 
      iDCs(Zol)-CIK and mDCs(Zol)-CIK cells treatment groups obtained 75% and 62.5% 
      long-term survival (>120 days) respectively, as compared with none of the control 
      animals or 37.5% treated with mDCs-CIK cells. CONCLUSION: Large numbers of CIK 
      cells with greater anti-tumor activities are rapidly generated by Zol-treated 
      iDCs/mDCs. This strategy is worthy of further investigation to improve adoptive 
      cell therapy against tumors.
FAU - Su, Xiaosan
AU  - Su X
AD  - Biomedical Research Center, The First Hospital of Kunming, Kunming 650011, 
      People's Republic of China. suxs163@163.com
FAU - Zhang, Lei
AU  - Zhang L
FAU - Jin, Liangkun
AU  - Jin L
FAU - Ye, Junsong
AU  - Ye J
FAU - Guan, Zheng
AU  - Guan Z
FAU - Chen, Rui
AU  - Chen R
LA  - eng
PT  - Journal Article
DEP - 20100615
PL  - Netherlands
TA  - J Clin Immunol
JT  - Journal of clinical immunology
JID - 8102137
RN  - 0 (Diphosphonates)
RN  - 0 (Imidazoles)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - 6XC1PAD3KF (Zoledronic Acid)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Coculture Techniques
MH  - Cytokine-Induced Killer Cells/immunology/*metabolism/pathology
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Dendritic Cells/*drug effects/immunology/metabolism/pathology
MH  - Diphosphonates/*pharmacology
MH  - Humans
MH  - Imidazoles/*pharmacology
MH  - Immunophenotyping
MH  - *Immunotherapy, Adoptive
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Mice, Nude
MH  - NK Cell Lectin-Like Receptor Subfamily K/antagonists & inhibitors/metabolism
MH  - Neoplasm Transplantation
MH  - Neoplasms, Experimental/*immunology/pathology/therapy
MH  - Zoledronic Acid
EDAT- 2010/06/16 06:00
MHDA- 2011/03/16 06:00
CRDT- 2010/06/16 06:00
PHST- 2010/04/06 00:00 [received]
PHST- 2010/05/27 00:00 [accepted]
PHST- 2010/06/16 06:00 [entrez]
PHST- 2010/06/16 06:00 [pubmed]
PHST- 2011/03/16 06:00 [medline]
AID - 10.1007/s10875-010-9434-1 [doi]
PST - ppublish
SO  - J Clin Immunol. 2010 Sep;30(5):766-74. doi: 10.1007/s10875-010-9434-1. Epub 2010 
      Jun 15.