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凯林肽与树突状细胞疫苗在4T-1小鼠乳腺癌模型中的协同抗肿瘤作用

Synergistic Antitumor Effects of Caerin Peptides and Dendritic Cell Vaccines in a 4T-1 Murine Breast Cancer Model.

作者信息

Mo Rongmi, Li Junjie, Song Xinyi, Fu Jiawei, Liu Mengqi, Luo Yuandong, Fu Quanlan, Wu Jinyi, Wu Hongyin, Liang Yongxin, Wang Tianfang, Liu Xiaosong, Ni Guoying

机构信息

The First Affiliated Hospital, Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou 510080, China.

Zhongao Biomedical Technology (Guangdong) Co., Ltd., Zhongshan 528400, China.

出版信息

Vaccines (Basel). 2025 May 28;13(6):577. doi: 10.3390/vaccines13060577.

DOI:10.3390/vaccines13060577
PMID:40573908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12197375/
Abstract

: Breast cancer remains a leading cause of cancer-related mortality among women worldwide, necessitating novel therapeutic strategies. This study aimed to investigate the synergistic antitumor effects of caerin peptides (F1/F3) combined with dendritic cell (DC) vaccines in a 4T-1 murine breast cancer model, providing new insights for breast cancer immunotherapy. : In vitro experiments evaluated the effects of F1/F3 on 4T-1 cell proliferation and apoptosis. A 4T-1 breast cancer mouse model was established, and treatments included F1/F3 alone, DC vaccines (DCV: loaded with whole tumor antigens; DCV: loaded with F1/F3-induced apoptotic antigens), or combination therapy. Flow cytometry analyzed immune cell subsets in the tumor microenvironment and lymph nodes, while ELISA measured cytokine levels. : F1/F3 significantly inhibited 4T-1 cell proliferation and induced apoptosis while suppressing tumor growth and lung metastasis in vivo. Flow cytometry revealed increased infiltration of CD4 T cells and cDC in tumors, along with reduced PD-L1 expression. DCV exhibited stronger T-cell proliferation induction and lower IL-10 secretion in vitro. Combination therapy with DCV and F1/F3 demonstrated superior tumor suppression compared to monotherapy. : F1/F3 enhances antitumor immunity by modulating the tumor microenvironment, and its combination with DCV yields synergistic effects. This study provides experimental evidence for combination immunotherapy in breast cancer, with potential for further optimization of DC vaccine design to improve efficacy.

摘要

乳腺癌仍然是全球女性癌症相关死亡的主要原因,因此需要新的治疗策略。本研究旨在探讨卡琳肽(F1/F3)与树突状细胞(DC)疫苗联合在4T-1小鼠乳腺癌模型中的协同抗肿瘤作用,为乳腺癌免疫治疗提供新的见解。

体外实验评估了F1/F3对4T-1细胞增殖和凋亡的影响。建立了4T-1乳腺癌小鼠模型,治疗方法包括单独使用F1/F3、DC疫苗(DCV:负载全肿瘤抗原;DCV:负载F1/F3诱导的凋亡抗原)或联合治疗。流式细胞术分析肿瘤微环境和淋巴结中的免疫细胞亚群,而酶联免疫吸附测定法测量细胞因子水平。

F1/F3显著抑制4T-1细胞增殖并诱导凋亡,同时在体内抑制肿瘤生长和肺转移。流式细胞术显示肿瘤中CD4 T细胞和cDC浸润增加,同时PD-L1表达降低。DCV在体外表现出更强的T细胞增殖诱导作用和更低的IL-10分泌。与单药治疗相比,DCV和F1/F3联合治疗显示出更好的肿瘤抑制效果。

F1/F3通过调节肿瘤微环境增强抗肿瘤免疫力,其与DCV联合产生协同效应。本研究为乳腺癌联合免疫治疗提供了实验证据,有望进一步优化DC疫苗设计以提高疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/8a68976e67e8/vaccines-13-00577-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/b59b37000880/vaccines-13-00577-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/fdb907bc5b73/vaccines-13-00577-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/f7d51e0bbe41/vaccines-13-00577-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/4e5b522849e9/vaccines-13-00577-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/8a68976e67e8/vaccines-13-00577-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/04a9d368576d/vaccines-13-00577-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/0165dd6d421e/vaccines-13-00577-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/fd14b3ade6d5/vaccines-13-00577-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/4535791d7bcb/vaccines-13-00577-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/edf7a0d9270d/vaccines-13-00577-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/fdb907bc5b73/vaccines-13-00577-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/f7d51e0bbe41/vaccines-13-00577-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/12197375/8a68976e67e8/vaccines-13-00577-g010.jpg

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Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine IFNα and is enhanced by CD47 blockade.Caerin 1.1/1.9介导的抗肿瘤免疫依赖于肿瘤浸润巨噬细胞通过自分泌IFNα的IFNAR-Stat1信号传导,并通过CD47阻断得以增强。
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