HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment

Background/Objectives: Effectively targeting treatment-resistant tumor cells, particularly cancer stem cells (CSCs) involved in tumor recurrence, remains a major challenge in immunotherapy. This study examines the potential of combining mechanical high-intensity focused ultrasound (M-HIFU) with dend...

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Main Authors: Bum-Seo Baek, Hyunmi Park, Ji-Woong Choi, Eun-Young Lee, Seung-Yong Seong
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/17/1/65
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author Bum-Seo Baek
Hyunmi Park
Ji-Woong Choi
Eun-Young Lee
Seung-Yong Seong
author_facet Bum-Seo Baek
Hyunmi Park
Ji-Woong Choi
Eun-Young Lee
Seung-Yong Seong
author_sort Bum-Seo Baek
collection DOAJ
description Background/Objectives: Effectively targeting treatment-resistant tumor cells, particularly cancer stem cells (CSCs) involved in tumor recurrence, remains a major challenge in immunotherapy. This study examines the potential of combining mechanical high-intensity focused ultrasound (M-HIFU) with dendritic cell (DC) vaccines to enhance immune responses against OLFM4-expressing tumors, a CSC marker linked to immune evasion and tumor growth. Methods: M-HIFU was applied to induce immunogenic cell death by mechanically disrupting tumor cells, releasing tumor-associated antigens and creating an immunostimulatory environment. DC vaccines loaded with OLFM4 were then administered to boost the immune response within this primed environment. Results: The combination of M-HIFU and DC vaccine significantly inhibited tumor growth and metastasis, with enhanced T-cell activation and increased recruitment of immune cells due to elevated chemokines CCL19 and CCL21. This synergy promoted immune memory, reducing the likelihood of recurrence. Conclusions: M-HIFU effectively promotes the migration of DC vaccines through CCL19/21, presenting a promising approach for cancer treatment. Further studies are recommended to optimize this combination for clinical applications, with potential to improve patient outcomes in challenging cancer types.
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spelling doaj-art-31cde5553fd746de932c21e09bd18e442025-01-24T13:45:47ZengMDPI AGPharmaceutics1999-49232025-01-011716510.3390/pharmaceutics17010065HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor MicroenvironmentBum-Seo Baek0Hyunmi Park1Ji-Woong Choi2Eun-Young Lee3Seung-Yong Seong4Wide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon 25159, Gangwon, Republic of KoreaWide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon 25159, Gangwon, Republic of KoreaWide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon 25159, Gangwon, Republic of KoreaWide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon 25159, Gangwon, Republic of KoreaWide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon 25159, Gangwon, Republic of KoreaBackground/Objectives: Effectively targeting treatment-resistant tumor cells, particularly cancer stem cells (CSCs) involved in tumor recurrence, remains a major challenge in immunotherapy. This study examines the potential of combining mechanical high-intensity focused ultrasound (M-HIFU) with dendritic cell (DC) vaccines to enhance immune responses against OLFM4-expressing tumors, a CSC marker linked to immune evasion and tumor growth. Methods: M-HIFU was applied to induce immunogenic cell death by mechanically disrupting tumor cells, releasing tumor-associated antigens and creating an immunostimulatory environment. DC vaccines loaded with OLFM4 were then administered to boost the immune response within this primed environment. Results: The combination of M-HIFU and DC vaccine significantly inhibited tumor growth and metastasis, with enhanced T-cell activation and increased recruitment of immune cells due to elevated chemokines CCL19 and CCL21. This synergy promoted immune memory, reducing the likelihood of recurrence. Conclusions: M-HIFU effectively promotes the migration of DC vaccines through CCL19/21, presenting a promising approach for cancer treatment. Further studies are recommended to optimize this combination for clinical applications, with potential to improve patient outcomes in challenging cancer types.https://www.mdpi.com/1999-4923/17/1/65mechanical high-intensity focused ultrasoundtumor microenvironmentcancer immunotherapydendritic cell vaccines
spellingShingle Bum-Seo Baek
Hyunmi Park
Ji-Woong Choi
Eun-Young Lee
Seung-Yong Seong
HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment
Pharmaceutics
mechanical high-intensity focused ultrasound
tumor microenvironment
cancer immunotherapy
dendritic cell vaccines
title HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment
title_full HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment
title_fullStr HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment
title_full_unstemmed HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment
title_short HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment
title_sort hifu ccl19 21 axis enhances dendritic cell vaccine efficacy in the tumor microenvironment
topic mechanical high-intensity focused ultrasound
tumor microenvironment
cancer immunotherapy
dendritic cell vaccines
url https://www.mdpi.com/1999-4923/17/1/65
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AT jiwoongchoi hifuccl1921axisenhancesdendriticcellvaccineefficacyinthetumormicroenvironment
AT eunyounglee hifuccl1921axisenhancesdendriticcellvaccineefficacyinthetumormicroenvironment
AT seungyongseong hifuccl1921axisenhancesdendriticcellvaccineefficacyinthetumormicroenvironment