PMID- 31052575
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 11
IP  - 5
DP  - 2019 May 2
TI  - mTOR Inhibitors Can Enhance the Anti-Tumor Effects of DNA Vaccines through 
      Modulating Dendritic Cell Function in the Tumor Microenvironment.
LID - 10.3390/cancers11050617 [doi]
LID - 617
AB  - The life span of dendritic cells (DCs) can become short following induced 
      activation, which is associated with metabolic transition due to the regulation 
      of mechanistic target of rapamycin (mTOR). The purpose of this study was to 
      investigate the potential of inhibiting mTOR to modulate DC functions for 
      elevating the anti-tumor effects of DNA vaccines. Therefore, the influences of 
      various inhibitors of mTOR (mTORi) on the expressions of DC maturation markers, 
      the abilities of antigen presenting and processing of BMM-derived DCs and the 
      tumor killing effects of E7-specific CD8(+) T lymphocytes activated by 
      BMM-derived DCs were in vitro examined. The anti-tumor effects of connective 
      tissue growth factor (CTGF)/E7 DNA vaccine and/or mTORi were also in vivo 
      analyzed. In our study, suppressive effects of mTORi on the DC maturation markers 
      expressed on BMMCs could be reversed. The mTORi-treated mature BMM-derived DCs 
      tended to be non-apoptotic. These mTORi-treated BMM-derived DCs could have better 
      antigen presenting and processing abilities. The E7-specific cytotoxic CD8+ T 
      lymphocytes could have more potent tumoricidal activity following activation of 
      mTORi-treated BMM-derived DCs. For tumor-bearing mice, those treated with CTGF/E7 
      DNA vaccine and mTORi indeed can have higher percentages of mature DCs in the 
      TME, better disease control and longer survivals. Consequently, application of 
      mTORi can be a pharmacological approach for temporally increasing life span, 
      antigen presenting and antigen processing of DCs to strengthen the therapeutic 
      outcome of cancer immunotherapy.
FAU - Chen, Yu-Li
AU  - Chen YL
AD  - Department of Obstetrics and Gynecology, College of Medicine, National Taiwan 
      University, Taipei City 100, Taiwan. uly1007@yahoo.com.tw.
FAU - Lin, Han-Wei
AU  - Lin HW
AD  - Graduate Institute of Oncology, College of Medicine, National Taiwan University, 
      Taipei City 100, Taiwan. handway_rc@hotmail.com.
FAU - Sun, Nai-Yun
AU  - Sun NY
AD  - Graduate Institute of Oncology, College of Medicine, National Taiwan University, 
      Taipei City 100, Taiwan. naiyunsun@gmail.com.
FAU - Yie, Jr-Chi
AU  - Yie JC
AD  - Department of Medicine, National Taiwan University Hospital Jin-Shan Branch, New 
      Taipei City 20844, Taiwan. yiejrchi@gmail.com.
AD  - Department of Anesthesiology, College of Medicine, National Taiwan University, 
      Taipei City 100, Taiwan. yiejrchi@gmail.com.
FAU - Hung, Hsueh-Chih
AU  - Hung HC
AD  - Department of Obstetrics and Gynecology, College of Medicine, National Taiwan 
      University, Taipei City 100, Taiwan. r05423018@ntu.edu.tw.
FAU - Chen, Chi-An
AU  - Chen CA
AD  - Department of Obstetrics and Gynecology, College of Medicine, National Taiwan 
      University, Taipei City 100, Taiwan. chianchen@ntu.edu.tw.
FAU - Sun, Wei-Zen
AU  - Sun WZ
AUID- ORCID: 0000-0001-8543-2600
AD  - Department of Anesthesiology, College of Medicine, National Taiwan University, 
      Taipei City 100, Taiwan. wzsun@ntu.edu.tw.
AD  - Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan 
      University, Taipei City 100, Taiwan. wzsun@ntu.edu.tw.
FAU - Cheng, Wen-Fang
AU  - Cheng WF
AD  - Department of Obstetrics and Gynecology, College of Medicine, National Taiwan 
      University, Taipei City 100, Taiwan. wenfangcheng@yahoo.com.
AD  - Graduate Institute of Oncology, College of Medicine, National Taiwan University, 
      Taipei City 100, Taiwan. wenfangcheng@yahoo.com.
AD  - Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan 
      University, Taipei City 100, Taiwan. wenfangcheng@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20190502
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC6562783
OTO - NOTNLM
OT  - DNA vaccine
OT  - dendritic cells
OT  - mTOR inhibitor
OT  - tumor microenvironment
COIS- The authors declare no conflict of interest.
EDAT- 2019/05/06 06:00
MHDA- 2019/05/06 06:01
PMCR- 2019/05/02
CRDT- 2019/05/05 06:00
PHST- 2019/04/16 00:00 [received]
PHST- 2019/04/25 00:00 [revised]
PHST- 2019/05/01 00:00 [accepted]
PHST- 2019/05/05 06:00 [entrez]
PHST- 2019/05/06 06:00 [pubmed]
PHST- 2019/05/06 06:01 [medline]
PHST- 2019/05/02 00:00 [pmc-release]
AID - cancers11050617 [pii]
AID - cancers-11-00617 [pii]
AID - 10.3390/cancers11050617 [doi]
PST - epublish
SO  - Cancers (Basel). 2019 May 2;11(5):617. doi: 10.3390/cancers11050617.