PMID- 30056600
OWN - NLM
STAT- MEDLINE
DCOM- 20181012
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 67
IP  - 10
DP  - 2018 Oct
TI  - Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by 
      self-differentiated monocyte-derived dendritic cells.
PG  - 1579-1588
LID - 10.1007/s00262-018-2212-2 [doi]
AB  - Cholangiocarcinoma (CCA) is a cancer of the bile ducts that is associated with 
      poor prognosis and poor treatment outcome. Approximately one-third of CCA 
      patients can undergo surgery, but the recurrence rate is high and chemotherapy 
      often cannot satisfactorily prolong survival. Cellular immunotherapy based on 
      adoptive T-cell transfer is a potential treatment for CCA; however, the 
      development of this technology and the search for an appropriate tumor-associated 
      antigen are still ongoing. To enhance the cytotoxic activity of effector T cells 
      against CCA, we developed self-differentiated monocyte-derived dendritic cells 
      (SD-DC) presenting cAMP-dependent protein kinase type I-alpha regulatory subunit 
      (PRKAR1A), which is an overexpressed protein that plays a role in the regulation 
      of tumor growth to activate T cells for CCA cell killing. Dendritic cells (DCs) 
      transduced with lentivirus harboring tri-cistronic cDNA sequences (SD-DC-PR) 
      could produce granulocyte-macrophage colony-stimulating factor, interleukin-4, 
      and PRKAR1A. SD-DC showed similar phenotypes to those of DCs derived by 
      conventional method. Autologous effector T cells (CD3+, CD8+) activated by 
      SD-DC-PR exhibited greater cytotoxic activity against CCA than those activated by 
      conventionally-derived DCs. Effector T cells activated by SD-DC-PR killed 60% of 
      CCA cells at an effector-to-target ratio of 15:1, which is approximately twofold 
      greater than the cell killing performance of those stimulated with control DC. 
      The cytotoxic activities of effector T cells activated by SD-DC-PR against CCA 
      cells were significantly associated with the expression levels of PRKR1A in CCA 
      cells. This finding that SD-DC-PR effectively stimulated autologous effector T 
      cells to kill CCA cells may help to accelerate the development of novel therapies 
      for treating CCA.
FAU - Panya, Aussara
AU  - Panya A
AD  - Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 
      Thailand.
AD  - Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), 4th 
      Floor Siriraj Medical Research Center (SiMR), Faculty of Medicine Siriraj 
      Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, 
      Thailand.
AD  - Center of Excellence in Bioresources for Agriculture, Industry and Medicine, 
      Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.
FAU - Thepmalee, Chutamas
AU  - Thepmalee C
AD  - Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), 4th 
      Floor Siriraj Medical Research Center (SiMR), Faculty of Medicine Siriraj 
      Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, 
      Thailand.
AD  - Graduate Program in Immunology, Faculty of Medicine Siriraj Hospital, Mahidol 
      University, Bangkok, Thailand.
FAU - Sawasdee, Nunghathai
AU  - Sawasdee N
AD  - Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), 4th 
      Floor Siriraj Medical Research Center (SiMR), Faculty of Medicine Siriraj 
      Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, 
      Thailand.
FAU - Sujjitjoon, Jatuporn
AU  - Sujjitjoon J
AD  - Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), 4th 
      Floor Siriraj Medical Research Center (SiMR), Faculty of Medicine Siriraj 
      Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, 
      Thailand.
FAU - Phanthaphol, Nattaporn
AU  - Phanthaphol N
AD  - Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), 4th 
      Floor Siriraj Medical Research Center (SiMR), Faculty of Medicine Siriraj 
      Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, 
      Thailand.
AD  - Graduate Program in Immunology, Faculty of Medicine Siriraj Hospital, Mahidol 
      University, Bangkok, Thailand.
FAU - Junking, Mutita
AU  - Junking M
AD  - Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), 4th 
      Floor Siriraj Medical Research Center (SiMR), Faculty of Medicine Siriraj 
      Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, 
      Thailand.
FAU - Wongkham, Sopit
AU  - Wongkham S
AD  - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 
      Thailand.
AD  - Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, 
      Khon Kaen, Thailand.
FAU - Yenchitsomanus, Pa-Thai
AU  - Yenchitsomanus PT
AD  - Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), 4th 
      Floor Siriraj Medical Research Center (SiMR), Faculty of Medicine Siriraj 
      Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, 
      Thailand. pathai.yen@mahidol.ac.th.
LA  - eng
GR  - R016010006/Mahidol University/
GR  - IRG5980006/Thailand Research Fund (TRF)/
GR  - IRN58W0001/International Research Network (IRN) under Thailand Research Fund 
      (TRF)/
GR  - PHD/0044/2556/TRF-Royal Golden Jubilee (RGJ)-Ph.D. Scholarship/
GR  - IRN5801PHDW03/TRF-IRN Scholarship/
GR  - TRG5780173/TRF Grant for New Researcher/
PT  - Journal Article
DEP - 20180728
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Cyclic AMP-Dependent Protein Kinase RIalpha Subunit)
RN  - 0 (PRKAR1A protein, human)
SB  - IM
MH  - Bile Duct Neoplasms/*immunology/metabolism/therapy
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Cholangiocarcinoma/*immunology/metabolism/therapy
MH  - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/immunology/metabolism
MH  - Dendritic Cells/cytology/*immunology
MH  - Genetic Vectors
MH  - Humans
MH  - *Immunotherapy
MH  - Monocytes/cytology/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
PMC - PMC11028072
OTO - NOTNLM
OT  - Cellular immunotherapy
OT  - Cholangiocarcinoma
OT  - Cytotoxic T cells
OT  - Dendritic cells
OT  - Self-differentiated monocyte-derived dendritic cells
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2018/07/30 06:00
MHDA- 2018/10/13 06:00
PMCR- 2018/07/28
CRDT- 2018/07/30 06:00
PHST- 2017/11/23 00:00 [received]
PHST- 2018/07/17 00:00 [accepted]
PHST- 2018/07/30 06:00 [pubmed]
PHST- 2018/10/13 06:00 [medline]
PHST- 2018/07/30 06:00 [entrez]
PHST- 2018/07/28 00:00 [pmc-release]
AID - 10.1007/s00262-018-2212-2 [pii]
AID - 2212 [pii]
AID - 10.1007/s00262-018-2212-2 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2018 Oct;67(10):1579-1588. doi: 
      10.1007/s00262-018-2212-2. Epub 2018 Jul 28.