Modulated electro-hyperthermia therapy combined with Korean mistletoe extract treatment exerts a strong anti-tumor activity by enhancing cellular and humoral immune responses in mice
Electro-hyperthermia therapy (EHT) has been known to cause temperature-dependent cell death and enhance the effects of conventional antitumor treatments, such as chemotherapy and radiotherapy. Furthermore, EHT modulates the innate and adaptive immune systems. Mistletoe is one of the most broadly stu...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Animal Cells and Systems |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19768354.2025.2470455 |
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| author | Yebeen Kim Jinwoo Hur Sung-Chul Hong Jaewoon Jung Choon-Ho Park Joon Beom Park Taek Joon Yoon Jong Bae Kim Seung-Hoon Yang |
| author_facet | Yebeen Kim Jinwoo Hur Sung-Chul Hong Jaewoon Jung Choon-Ho Park Joon Beom Park Taek Joon Yoon Jong Bae Kim Seung-Hoon Yang |
| author_sort | Yebeen Kim |
| collection | DOAJ |
| description | Electro-hyperthermia therapy (EHT) has been known to cause temperature-dependent cell death and enhance the effects of conventional antitumor treatments, such as chemotherapy and radiotherapy. Furthermore, EHT modulates the innate and adaptive immune systems. Mistletoe is one of the most broadly studied complementary and alternative therapeutic agents for cancer treatment due to its ability to stimulate the immune systems. This study aimed to investigate the effects of EHT and mistletoe therapy combination on immune responses. Tumors induced by B16-BL6 melanoma cells were treated twice with modulated EHT (mEHT) (43°C for 10 or 20 min) and with intravenous injection of a Korean mistletoe extract (KME). We examined the level of interferon (IFN)-γ, granzyme, interleukin (IL)-2, IL-10, and tumor-specific antibodies using enzyme-linked immunosorbent assay methods to further study the immunological responses in the combination of mEHT and KME. Additionally, cytotoxic T lymphocyte (CTL) activity is investigated. In this study, we revealed a significant anti-tumor immunological activity elevation in tumor-bearing mice by combined mEHT and KME therapy. Specifically, the combination of mEHT and KME treatment was effective in inhibiting tumor growth in mice. The combination treatment elicited CTL immune response and increased IFN-γ and granzyme secretion. Particularly, the co-treatment appeared to efficiently suppress the immune signal related to tumor-associated macrophage differentiation. Importantly, tumor cell-specific antibodies could be induced in mice after mEHT-treated tumor cell immunization, which represent a promising cancer vaccine strategy. Thus, our results indicate the therapeutic actions of KME as a feasible partner of mEHT, suggesting its potential candidate for cancer immunotherapy.Abbreviations: APC, Antigen-presenting cell; CTL, Cytotoxic T lymphocyte; EHT, Electro-hyperthermia therapy; ELISA, Enzyme-linked immunosorbent assay; HSP, Heat shock protein; KME, Korean mistletoe extract; NK, Natural killer; PBS, Phosphate-buffered saline; QOL, Quality of life; RF, Radio-frequency; TAM, Tumor-associated macrophage |
| format | Article |
| id | doaj-art-7e220543f78e4a1cac2f122541663c9b |
| institution | Kabale University |
| issn | 1976-8354 2151-2485 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Animal Cells and Systems |
| spelling | doaj-art-7e220543f78e4a1cac2f122541663c9b2025-08-20T03:48:11ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852025-12-0129116317210.1080/19768354.2025.2470455Modulated electro-hyperthermia therapy combined with Korean mistletoe extract treatment exerts a strong anti-tumor activity by enhancing cellular and humoral immune responses in miceYebeen Kim0Jinwoo Hur1Sung-Chul Hong2Jaewoon Jung3Choon-Ho Park4Joon Beom Park5Taek Joon Yoon6Jong Bae Kim7Seung-Hoon Yang8Department of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul, Republic of KoreaDepartment of Food and Nutrition, Yuhan University, Buchoen, Republic of KoreaDepartment of Food Science and Biotechnology, Kunsan National University, Kunsan, Republic of KoreaDepartment of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul, Republic of KoreaGraduate School of Clinical Pharmacy and Pharmaceutics, Ajou University, Suwon, South KoreaMistletoe Research Center, New Breath Hospital, Seoul, Republic of KoreaDoGenBio Co., Ltd., Seoul, Republic of KoreaMistletoe Research Center, New Breath Hospital, Seoul, Republic of KoreaDepartment of Biomedical Engineering, College of Life Science and Biotechnology, Dongguk University, Seoul, Republic of KoreaElectro-hyperthermia therapy (EHT) has been known to cause temperature-dependent cell death and enhance the effects of conventional antitumor treatments, such as chemotherapy and radiotherapy. Furthermore, EHT modulates the innate and adaptive immune systems. Mistletoe is one of the most broadly studied complementary and alternative therapeutic agents for cancer treatment due to its ability to stimulate the immune systems. This study aimed to investigate the effects of EHT and mistletoe therapy combination on immune responses. Tumors induced by B16-BL6 melanoma cells were treated twice with modulated EHT (mEHT) (43°C for 10 or 20 min) and with intravenous injection of a Korean mistletoe extract (KME). We examined the level of interferon (IFN)-γ, granzyme, interleukin (IL)-2, IL-10, and tumor-specific antibodies using enzyme-linked immunosorbent assay methods to further study the immunological responses in the combination of mEHT and KME. Additionally, cytotoxic T lymphocyte (CTL) activity is investigated. In this study, we revealed a significant anti-tumor immunological activity elevation in tumor-bearing mice by combined mEHT and KME therapy. Specifically, the combination of mEHT and KME treatment was effective in inhibiting tumor growth in mice. The combination treatment elicited CTL immune response and increased IFN-γ and granzyme secretion. Particularly, the co-treatment appeared to efficiently suppress the immune signal related to tumor-associated macrophage differentiation. Importantly, tumor cell-specific antibodies could be induced in mice after mEHT-treated tumor cell immunization, which represent a promising cancer vaccine strategy. Thus, our results indicate the therapeutic actions of KME as a feasible partner of mEHT, suggesting its potential candidate for cancer immunotherapy.Abbreviations: APC, Antigen-presenting cell; CTL, Cytotoxic T lymphocyte; EHT, Electro-hyperthermia therapy; ELISA, Enzyme-linked immunosorbent assay; HSP, Heat shock protein; KME, Korean mistletoe extract; NK, Natural killer; PBS, Phosphate-buffered saline; QOL, Quality of life; RF, Radio-frequency; TAM, Tumor-associated macrophagehttps://www.tandfonline.com/doi/10.1080/19768354.2025.2470455Electro-hyperthermiamistletoe therapyB16-BL6 melanomatumor-specific antibodiescancer vaccine |
| spellingShingle | Yebeen Kim Jinwoo Hur Sung-Chul Hong Jaewoon Jung Choon-Ho Park Joon Beom Park Taek Joon Yoon Jong Bae Kim Seung-Hoon Yang Modulated electro-hyperthermia therapy combined with Korean mistletoe extract treatment exerts a strong anti-tumor activity by enhancing cellular and humoral immune responses in mice Animal Cells and Systems Electro-hyperthermia mistletoe therapy B16-BL6 melanoma tumor-specific antibodies cancer vaccine |
| title | Modulated electro-hyperthermia therapy combined with Korean mistletoe extract treatment exerts a strong anti-tumor activity by enhancing cellular and humoral immune responses in mice |
| title_full | Modulated electro-hyperthermia therapy combined with Korean mistletoe extract treatment exerts a strong anti-tumor activity by enhancing cellular and humoral immune responses in mice |
| title_fullStr | Modulated electro-hyperthermia therapy combined with Korean mistletoe extract treatment exerts a strong anti-tumor activity by enhancing cellular and humoral immune responses in mice |
| title_full_unstemmed | Modulated electro-hyperthermia therapy combined with Korean mistletoe extract treatment exerts a strong anti-tumor activity by enhancing cellular and humoral immune responses in mice |
| title_short | Modulated electro-hyperthermia therapy combined with Korean mistletoe extract treatment exerts a strong anti-tumor activity by enhancing cellular and humoral immune responses in mice |
| title_sort | modulated electro hyperthermia therapy combined with korean mistletoe extract treatment exerts a strong anti tumor activity by enhancing cellular and humoral immune responses in mice |
| topic | Electro-hyperthermia mistletoe therapy B16-BL6 melanoma tumor-specific antibodies cancer vaccine |
| url | https://www.tandfonline.com/doi/10.1080/19768354.2025.2470455 |
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