基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Synergistic Antitumor Effects of Caerin Peptides and Dendritic Cell Vaccines in a 4T-1 Murine Breast Cancer Model.
Synergistic Antitumor Effects of Caerin Peptides and Dendritic Cell Vaccines in a 4T-1 Murine Breast Cancer Model.
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体外实验评估F1/F3对4T-1细胞增殖和凋亡的影响。建立4T-1乳腺癌小鼠模型,治疗包括单独F1/F3、DC疫苗(DCV 1:负载全肿瘤抗原;DCV 2: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,ELISA测定细胞因子水平。
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 1浸润增加,同时PD-L1表达降低。DCV 2在体外表现出更强的T细胞增殖诱导能力和更低的IL-10分泌。DCV 2与F1/F3联合治疗相比单药治疗表现出更优的肿瘤抑制作用。
F1/F3通过调节肿瘤微环境增强抗肿瘤免疫,其与DCV 2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,并具有进一步优化DC疫苗设计以提高疗效的潜力。
Background/Objectives : 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. Methods : 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 1 : loaded with whole tumor antigens; DCV 2 : 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.
Results : 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 1 in tumors, along with reduced PD-L1 expression.
DCV 2 exhibited stronger T-cell proliferation induction and lower IL-10 secretion in vitro. Combination therapy with DCV 2 and F1/F3 demonstrated superior tumor suppression compared to monotherapy. Conclusions : F1/F3 enhances antitumor immunity by modulating the tumor microenvironment, and its combination with DCV 2 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.
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