Published online Aug 7, 2019. doi: 10.3748/wjg.v25.i29.3941
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
Cholangiocarcinoma (CCA) is a biliary tract malignancy. As no specific biomarkers are available, CCA patients frequently present with a disseminated tumour too late for curative treatment. Honokiol is a hydroxylated biphenyl compound isolated from Magnolia offinalis. Many studies have reported that honokiol has anti-tumour properties on various types of cancer by induction of cell apoptosis. A dendritic cell (DC)-based cancer vaccine is a vaccine that aims to stimulate anticancer immunity in patients through the capacity to activate tumour-specific T cells. However, pulsing DCs with whole tumour cell lysates have shown low efficacy against CCA cells in vitro.
Evidence suggests that the efficacy of DC-based cancer vaccines on CCA is low, especially DCs loaded with tumour cell lysates strategy. In addition, the anti-tumour activity of honokiol could be due to the induction of cancer cell apoptosis. This effect may be associated with the release of damage-associated molecular patterns (DAMPs) from cancer cells, which increases the immunogenicity of tumour antigens. Therefore, the authors of this study were interested in the construction of DCs loaded with cell lysates derived from honokiol-treated CCA tumour cells with the aim of eliciting apoptosis in tumour cells as well as creating a broad array of TTAs in the form of dead and dying cells.
The aim of this study was to maximise the anti-tumour activities of DCs loaded with cell lysates from honokiol-treated CCA cells.
Anti-tumour activity of honokiol was studied, including the cytotoxicity and cell apoptosis assay. The effects of honokiol on DAMPs expression from CCA cells were also investigated. Then, CCA cells with or without honokiol treatments were derived to obtain tumour cell lysates used to pulse the DC cells, after which the latter were used to further stimulate T cells. Finally, the stimulated T cells were exposed to CCA cells and the killing of CCA cells by T cells was determined.
The data showed that honokiol was cytotoxic to human CCA cells KKU-213L5 via intrinsic or extrinsic apoptotic pathways. Interestingly, the induction of cell apoptosis by honokiol was associated with DAMPs release, including HMGB1 and HSP90. DCs loaded with tumour lysates derived from honokiol-treated KKU-213L5 cells enhanced priming and stimulated T lymphocyte proliferation as well as type I cytokine production. Importantly, T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells, which significantly increased the specific killing of human CCA cells compared to those associated with DCs pulsed with cell lysates of untreated CCA cells.
These findings provide new evidence that honokiol may have anticancer properties against CCA cells. Further, honokiol may possess the potential to enhance DC-based cancer vaccines, most probably by enhancing the immunogenicity of CCA, which further promotes DCs and T cell stimulation.
Our model showed the improvement of cancer vaccine efficacy against CCA based on DCs and demonstrated the use of honokiol as a herbal-derived compound in combination with tumour antigen pulsed DCs to maximise the antitumour response of cytotoxic antitumour T lymphocytes.