Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2019; 25(29): 3941-3955
Published online Aug 7, 2019. doi: 10.3748/wjg.v25.i29.3941
Honokiol-enhanced cytotoxic T lymphocyte activity against cholangiocarcinoma cells mediated by dendritic cells pulsed with damage-associated molecular patterns
Arunya Jiraviriyakul, Worawat Songjang, Pongsathorn Kaewthet, Phachsita Tanawatkitichai, Punyapat Bayan, Sutatip Pongcharoen
Arunya Jiraviriyakul, Worawat Songjang, Sutatip Pongcharoen, Biomedical Science Graduate School, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
Arunya Jiraviriyakul, Worawat Songjang, Pongsathorn Kaewthet, Phachsita Tanawatkitichai, Punyapat Bayan, Department of Medical technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
Sutatip Pongcharoen, Division of Immunology, Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand
Sutatip Pongcharoen, Research Centre of Academic Excellence in Petroleum, Petrochemical, and Advanced Materials, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand
Sutatip Pongcharoen, Centre of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand
Author contributions: Jiraviriyakul A and Pongcharoen S conceived the study; Jiraviriyakul A, Songjang W, Kaewthet P, Tanawatkitichai P and Bayan P performed experiments; Jiraviriyakul A, Songjang W and Pongcharoen S wrote the manuscript.
Supported by the grant from the Thailand Research Fund, No. BRG6180010; and Naresuan University Research Grant, No. R2561B001.
Institutional review board statement: The study was reviewed and approved by the Naresuan University Institutional Review Board.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sutatip Pongcharoen, MD, PhD, Division of Immunology, Department of Medicine, Faculty of Medicine, Naresuan University, Tapho District, Muang, Phitsanulok 65000, Thailand. sutatipp@nu.ac.th
Telephone: +66-89-5628060
Received: March 29, 2019
Peer-review started: March 29, 2019
First decision: June 10, 2019
Revised: June 21, 2019
Accepted: July 5, 2019
Article in press: July 5, 2019
Published online: August 7, 2019
Processing time: 131 Days and 22.6 Hours
Abstract
BACKGROUND

Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such anti-tumor activity can be increased using cell lysates derived from an honokiol-treated cholangiocarcinoma cell line (KKU-213L5).

AIM

To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5).

METHODS

The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated.

RESULTS

Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells.

CONCLUSION

The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.

Keywords: Cholangiocarcinoma; Dendritic cells; Honokiol; Damage-associated molecular patterns; Tumor cell lysates

Core tip: We constructed dendritic cells (DCs) loaded with cell lysates derived from honokiol-treated cholangiocarcinoma cells, with the aim of eliciting apoptosis in tumour cells and creating a broad array of tumour associated antigents in the form of dead and dying cells. Our data demonstrated that DCs primed with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells could improve the fuction of effector T lymphocytes in killing of the cancer cells. This suggested that honokiol enhanced the immunogenicity of cholangiocarcinoma antigens with increased effectiveness of DC-based vaccine formulation.