PMID- 26450924
OWN - NLM
STAT- MEDLINE
DCOM- 20160422
LR  - 20220317
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 473
IP  - 1
DP  - 2016 Jan 1
TI  - Co-operation of alpha-galactosylceramide-loaded tumour cells and TLR9 agonists induce 
      potent anti-tumour responses in a murine colon cancer model.
PG  - 7-19
LID - 10.1042/BJ20150129 [doi]
AB  - Dendritic cells (DCs) and invariant natural killer T (iNKT) cells play important 
      roles in linking innate immunity and adaptive immunity. Mature DCs activated by 
      Toll-like receptor (TLR) agonists directly activate iNKT cells and the iNKT 
      ligand alpha-galactosylceramide (alpha-Galcer) can induce DC maturation, resulting in 
      enhanced protective immune responses. In the present study, we aimed to boost 
      anti-tumour immunity in a murine colon cancer model by synergizing DCs and iNKT 
      cells using alpha-Galcer-loaded tumour cells (tumour-Gal) and the TLR9 agonist 
      cytosine-phosphorothioate-guanine (CpG1826). The vaccine strategy was sufficient 
      to inhibit growth of established tumours and prolonged survival of tumour-bearing 
      mice. Importantly, the immunization induced an adaptive memory immune response as 
      the survivors from primary tumour inoculations were resistant to a tumour 
      re-challenge. Furthermore, injection of tumour-Gal with CpG1826 resulted in iNKT 
      cell activation and DC maturation as defined by interferon (IFN)-gamma secretion by 
      iNKT, natural killer (NK) cells and interleukin (IL)-12 by DCs. 
      Immunohistochemistry analysis revealed that cluster of differentiation (CD)4(+) 
      T-cells and CD8(+) T-cells played important roles in anti-tumour immunity. 
      Additionally, the vaccine redirected Th2 (T-helper cell type 2) responses toward 
      Th1 (T-helper cell type 1) responses with increases in IL-2, IFN-gamma expression and 
      decreases in IL-4 and IL-5 expression after immunization with tumour-Gal with 
      CpG1826. Taken together, our results demonstrated a novel vaccination by 
      synergizing tumour-Gal and CpG1826 against murine colon cancer, which can be 
      further developed as tumour-specific immunotherapy against human cancer.
CI  - (c) 2016 Authors; published by Portland Press Limited.
FAU - Dong, Tiangeng
AU  - Dong T
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China.
FAU - Yi, Tuo
AU  - Yi T
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China.
FAU - Yang, Mengxuan
AU  - Yang M
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China.
FAU - Lin, Shengli
AU  - Lin S
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China.
FAU - Li, Wenxiang
AU  - Li W
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China.
FAU - Xu, Xingyuan
AU  - Xu X
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China.
FAU - Hu, Jianwei
AU  - Hu J
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China.
FAU - Jia, Lijun
AU  - Jia L
AD  - Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, 
      China Department of Oncology, Shanghai Medical College, Fudan University, 
      Shanghai, 200032, China.
FAU - Hong, Xinqiang
AU  - Hong X
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China hong.xinqiang@zs-hospital.sh.cn 
      niu.weixin@zs-hospital.sh.cn.
FAU - Niu, Weixin
AU  - Niu W
AD  - Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Feng-Lin 
      Road, Shanghai, 200032, China hong.xinqiang@zs-hospital.sh.cn 
      niu.weixin@zs-hospital.sh.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151008
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Galactosylceramides)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (alpha-galactosylceramide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage
MH  - Cancer Vaccines/*administration & dosage
MH  - Coculture Techniques
MH  - Colonic Neoplasms/pathology/*prevention & control
MH  - *Disease Models, Animal
MH  - Female
MH  - Galactosylceramides/*administration & dosage
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Toll-Like Receptor 9/*agonists
MH  - Treatment Outcome
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - Toll-like receptor 9
OT  - colon cancer
OT  - dendritic cells
OT  - invariant natural killer T (iNKT) cells
OT  - therapeutic vaccine
EDAT- 2015/10/10 06:00
MHDA- 2016/04/23 06:00
CRDT- 2015/10/10 06:00
PHST- 2015/02/02 00:00 [received]
PHST- 2015/10/08 00:00 [accepted]
PHST- 2015/10/10 06:00 [entrez]
PHST- 2015/10/10 06:00 [pubmed]
PHST- 2016/04/23 06:00 [medline]
AID - BJ20150129 [pii]
AID - 10.1042/BJ20150129 [doi]
PST - ppublish
SO  - Biochem J. 2016 Jan 1;473(1):7-19. doi: 10.1042/BJ20150129. Epub 2015 Oct 8.