Amlodipine as an Immunomodulatory Agent in Cancer Therapy: Enhancing Dendritic Cell Activation in Combination with Tumor-associated Antigen.

IF 12 1区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Zhixuan Wang,Xinxuan Huang,Lifan Duan,Shujie Tian,Chenxi Shi,Yongbin Mou,Heng Dong,Yu Gao,Lixing Weng
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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.
氨氯地平作为肿瘤治疗中的免疫调节剂:与肿瘤相关抗原联合增强树突状细胞活化。
本研究探讨了广泛应用的降压药氨氯地平对树突状细胞(DC)成熟和抗肿瘤免疫的免疫调节作用。通过流式细胞术、ELISA和单细胞RNA测序,我们发现氨氯地平显著促进DC成熟,CD80和CD86表达增加,以及与T细胞活化相关的CCL4和Saa3等基因上调。此外,当氨氯地平与吲哚青绿(ICG)或阿霉素(DOX)联合应用于4T1乳腺癌和CT26结肠癌小鼠模型时,我们观察到CD8+ T细胞的显著活化。这种联合治疗还导致血清细胞因子水平升高,如TNF-α、IFN-γ和IL-12,以及CD8+效应记忆T细胞的上调,这表明强大的全身免疫激活,最终有助于抑制肿瘤生长和减少肺转移。我们的研究阐明了氨氯地平在促进DC成熟和抗肿瘤免疫反应中的免疫调节作用,为未来的癌症免疫治疗策略提供了一条有希望的途径,并值得在临床试验中进一步研究。
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来源期刊
Molecular Therapy
Molecular Therapy 医学-生物工程与应用微生物
CiteScore
19.20
自引率
3.20%
发文量
357
审稿时长
3 months
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.
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