Abstract
Background
Dendritic cell (DC) vaccine is a promising immunotherapy for hepatocellular carcinoma (HCC) via triggering antigen-specific anti-tumor immunity. Hypoxia contributes to higher level and broader spectrum of antigen expression in tumor cells.
Methods
This study aims to compare immunological activity and therapeutic efficacy between hypoxic and normoxic HCC cell line lysate-pulsed DC vaccines.
Results
The results showed that hypoxic HCC cell line lysate-pulsed DC vaccines exhibited a stronger activity in producing interleukin-12 and promoting T cell proliferation and cytotoxicity in vitro. In HCC mice, hypoxic HCC cell line lysate-pulsed DC vaccines displayed a better efficacy in improving survival time and tumor volume and inducing intratumoral cytotoxic T cell infiltration and activation as well as tumor cell apoptosis. Adenylate kinase 4-derived antigens were important for hypoxic HCC cell line lysate-pulsed DC vaccine-elicited T cell killing.
Conclusions
In conclusion, this study demonstrated hypoxic HCC cell line lysate-pulsed DC vaccine as a potential therapeutic strategy for HCC.
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Fig. 1: Generation and characterization of normoxic and hypoxic HCC cell lysate-pulsed DC vaccines.
Fig. 2: Hypoxic HCC cell lysate-pulsed DC vaccines exhibited a stronger capacity in producing IL-12 cytokine and inducing T cell proliferation and cytotoxicity than normoxic HCC cell lysate-pulsed DC vaccines.
Fig. 3: Hypoxic HCC cell lysate-pulsed DC vaccines displayed a greater potency in activating T cell-mediated killing of both normoxic and hypoxic HCC cells than normoxic HCC cell lysate-pulsed DC vaccines.
Fig. 4: Hypoxic HCC cell lysate-pulsed DC vaccination showed better efficacy in prolonging survival time in HCC mice than normoxic HCC cell lysate-pulsed DC vaccination.
Fig. 5: Hypoxic HCC cell lysate-pulsed DC vaccination showed better efficacy in reducing tumor volume in HCC mice than normoxic HCC cell lysate-pulsed DC vaccination.
Fig. 6: AK4-derived antigens were important for hypoxic HCC cell lysate-pulsed DC vaccine-induced T cell cytotoxicity against hypoxic HCC cells.
Data availability
All data needed to evaluate the conclusions in the paper are present in the paper and Supplementary Materials.
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Acknowledgements
This work was supported by a research grant from China Medical University Hospital, Taichung, Taiwan (grant number DMR-113-028; CFT). Experiments and data analysis were performed in part through the use of the Medical Research Core Facilities Center, Office of Research & Development at China Medical University, Taichung, Taiwan.
Funding
China Medical University Hospital, Taichung, Taiwan (grant number DMR-113-028; CFT).
Author information
Authors and Affiliations
Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan, ROC
Long-Bin Jeng & Chiao-Fang Teng
Department of Surgery, China Medical University Hospital, Taichung, Taiwan, ROC
Long-Bin Jeng
Cell Therapy Center, China Medical University Hospital, Taichung, Taiwan, ROC
Long-Bin Jeng
School of Medicine, China Medical University, Taichung, Taiwan, ROC
Long-Bin Jeng
Ph.D. Program for Biotech Pharmaceutical Industry, China Medical University, Taichung, Taiwan, ROC
Fu-Ying Shih
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, ROC
Yu-Wen Liao, Woei-Cherng Shyu & Chiao-Fang Teng
Translational Medicine Research Center, China Medical University Hospital, Taichung, 404, Taiwan, ROC
Woei-Cherng Shyu
Department of Neurology, China Medical University Hospital, Taichung, Taiwan, ROC
Woei-Cherng Shyu
Department of Occupational Therapy, Asia University, Taichung, Taiwan, ROC
Woei-Cherng Shyu
Master Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan, ROC
Chiao-Fang Teng
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Long-Bin Jeng
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Contributions
Conceptualization: CFT. Formal analysis: LBJ, FYS, YWL, WCS, CFT. Funding acquisition: CFT. Investigation: LBJ, FYS, YWL, WCS, CFT. Methodology: LBJ, FYS, YWL, WCS, CFT. Supervision: CFT. Visualization: CFT. Writing—original draft: CFT. Writing—review & editing: CFT.
Corresponding author
Correspondence to Chiao-Fang Teng.
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Ethics approval and consent to participate
All mouse experiments were performed under the approval of the Institutional Animal Care and Use Committee of China Medical University (Protocol No: CMUIACUC-2020-022) in accordance with the guidelines and regulations of the Animal Protection Act of the Council of Agriculture, Executive Yuan, Taiwan. No human experiments were conducted in this study.
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The authors declare no competing interests.
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Jeng, LB., Shih, FY., Liao, YW. et al. Hypoxic tumor cell line lysate-pulsed dendritic cell vaccine exhibits better therapeutic effects on hepatocellular carcinoma. Br J Cancer (2025). https://doi.org/10.1038/s41416-025-02975-w
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Received:23 November 2024
Revised:03 February 2025
Accepted:26 February 2025
Published:07 March 2025
DOI:https://doi.org/10.1038/s41416-025-02975-w
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