{"title":"Amlodipine as an Immunomodulatory Agent in Cancer Therapy: Enhancing Dendritic Cell Activation in Combination with Tumor-associated Antigen.","authors":"Zhixuan Wang,Xinxuan Huang,Lifan Duan,Shujie Tian,Chenxi Shi,Yongbin Mou,Heng Dong,Yu Gao,Lixing Weng","doi":"10.1016/j.ymthe.2025.07.030","DOIUrl":null,"url":null,"abstract":"This study explores the immunomodulatory effects of amlodipine, a widely used antihypertensive, on dendritic cell (DC) maturation and anti-tumor immunity. Using flow cytometry, ELISA, and single-cell RNA sequencing, we found that amlodipine significantly promotes DC maturation, evidenced by increased CD80 and CD86 expression and upregulation of genes like CCL4 and Saa3 related to T cell activation. Furthermore, when amlodipine was administered in conjunction with indocyanine green (ICG) or doxorubicin (DOX) therapy in murine models of 4T1 breast cancer and CT26 colon cancer, we observed a notable activation of CD8+ T cell. This combination therapy also resulted in elevated serum levels of cytokines such as TNF-α, IFN-γ, and IL-12, and the upregulation of CD8+ effector memory T cells indicative of a robust systemic immune activation, which ultimately contributed to the inhibition of tumor growth and a decrease in lung metastasis. Our research elucidates the immunomodulatory role of amlodipine in enhancing DC maturation and anti-tumor immune responses, suggesting a promising avenue for future cancer immunotherapy strategies and warranting further investigation in clinical trials.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"19 1","pages":""},"PeriodicalIF":12.0000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ymthe.2025.07.030","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
This study explores the immunomodulatory effects of amlodipine, a widely used antihypertensive, on dendritic cell (DC) maturation and anti-tumor immunity. Using flow cytometry, ELISA, and single-cell RNA sequencing, we found that amlodipine significantly promotes DC maturation, evidenced by increased CD80 and CD86 expression and upregulation of genes like CCL4 and Saa3 related to T cell activation. Furthermore, when amlodipine was administered in conjunction with indocyanine green (ICG) or doxorubicin (DOX) therapy in murine models of 4T1 breast cancer and CT26 colon cancer, we observed a notable activation of CD8+ T cell. This combination therapy also resulted in elevated serum levels of cytokines such as TNF-α, IFN-γ, and IL-12, and the upregulation of CD8+ effector memory T cells indicative of a robust systemic immune activation, which ultimately contributed to the inhibition of tumor growth and a decrease in lung metastasis. Our research elucidates the immunomodulatory role of amlodipine in enhancing DC maturation and anti-tumor immune responses, suggesting a promising avenue for future cancer immunotherapy strategies and warranting further investigation in clinical trials.
期刊介绍:
Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.