Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. 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...

Full description

Saved in:
Bibliographic Details
Main Authors: Aussara Panya, Chutamas Thepmalee, Nunghathai Sawasdee, Jatuporn Sujjitjoon, Nattaporn Phanthaphol, Mutita Junking, Sopit Wongkham, Pa thai Yenchitsomanus
Format: Journal
Published: 2018
Subjects:
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050819611&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/58342
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Chiang Mai University
id th-cmuir.6653943832-58342
record_format dspace
spelling th-cmuir.6653943832-583422018-09-05T04:36:57Z Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells Aussara Panya Chutamas Thepmalee Nunghathai Sawasdee Jatuporn Sujjitjoon Nattaporn Phanthaphol Mutita Junking Sopit Wongkham Pa thai Yenchitsomanus Biochemistry, Genetics and Molecular Biology Immunology and Microbiology Medicine © 2018, Springer-Verlag GmbH Germany, part of Springer Nature. 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. 2018-09-05T04:22:57Z 2018-09-05T04:22:57Z 2018-01-01 Journal 14320851 03407004 2-s2.0-85050819611 10.1007/s00262-018-2212-2 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050819611&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/58342
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
Immunology and Microbiology
Medicine
spellingShingle Biochemistry, Genetics and Molecular Biology
Immunology and Microbiology
Medicine
Aussara Panya
Chutamas Thepmalee
Nunghathai Sawasdee
Jatuporn Sujjitjoon
Nattaporn Phanthaphol
Mutita Junking
Sopit Wongkham
Pa thai Yenchitsomanus
Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
description © 2018, Springer-Verlag GmbH Germany, part of Springer Nature. 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.
format Journal
author Aussara Panya
Chutamas Thepmalee
Nunghathai Sawasdee
Jatuporn Sujjitjoon
Nattaporn Phanthaphol
Mutita Junking
Sopit Wongkham
Pa thai Yenchitsomanus
author_facet Aussara Panya
Chutamas Thepmalee
Nunghathai Sawasdee
Jatuporn Sujjitjoon
Nattaporn Phanthaphol
Mutita Junking
Sopit Wongkham
Pa thai Yenchitsomanus
author_sort Aussara Panya
title Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
title_short Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
title_full Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
title_fullStr Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
title_full_unstemmed Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
title_sort cytotoxic activity of effector t cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050819611&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/58342
_version_ 1681425047494852608