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
用塞来昔布处理的树突状细胞疫苗改善了动物乳腺癌模型中的细胞免疫反应
英文原题：Vaccination with celecoxib-treated dendritic cells improved cellular immune responses in an animal breast cancer model.
查看英文原题
Vaccination with celecoxib-treated dendritic cells improved cellular immune responses in an animal breast cancer model.
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研究概要
我们的研究结果表明，LPS/CXB 处理的 DC 疫苗在小鼠 BC 模型中有效调节了抗肿瘤免疫反应。
研究思路结论见上方概要
目的
前列腺素E2（PGE2）是花生四烯酸经环氧合酶（COX）途径代谢的产物，对树突状细胞（DC）活性具有抑制作用，从而抑制抗肿瘤免疫应答。因此，在DC疫苗制备过程中靶向COX可能增强DC介导的抗肿瘤应答。我们旨在研究用塞来昔布（CXB）——一种选择性COX2抑制剂——处理的DC疫苗对某些T细胞相关参数的影响。
方法
在BALB/c小鼠中诱导乳腺癌（BC），随后它们接受经脂多糖（LPS-mDCs）、LPS联合5 μM剂量CXB（LPS/CXB5-mDCs）和LPS联合10 μM剂量CXB（LPS/CXB10-mDCs）处理的DC疫苗。分别使用流式细胞术、ELISA和实时PCR测定脾脏Th1和Treg细胞的频率、脾细胞产生的IFN-γ、IL-12和TGF-β的量，以及肿瘤中Granzyme-B、T-bet和FOXP3的表达。
结果
与未治疗肿瘤组（T-control）相比，LPS/CXB5-mDCs和LPS/CXB10-mDCs治疗降低了肿瘤生长（P = 0.009和P < 0.0001），提高了生存率（P = 0.002），增加了脾脏Th1细胞的频率（P = 0.0872和P = 0.0155），增加了脾细胞产生IFN-γ（P = 0.0003和P = 0.0061）和IL-12（P = 0.001和P = 0.0009），上调了T-bet（P = 0.062和P < 0.0001）和Granzyme-B（P = 0.0448和P = 0.4485），而与T-control组相比，Treg细胞数量减少（P = 0.0014和P = 0.0219），脾细胞产生TGF-β的量减少（P = 0.0535和P = 0.0169），FOXP3表达降低（P = 0.0006和P = 0.0057）。
展开英文摘要原文
PURPOSE
Prostaglandin E2 (PGE2), a product of cyclooxygenase (COX) pathway of arachidonic acid, exerts inhibitory impacts on dendritic cell (DC) activity to repress anti-tumor immune responses. Therefore, targeting COX during DC vaccine generation may enhance DC-mediated antitumor responses. We aimed to investigate the impacts of DC vaccine treated with celecoxib (CXB), a selective COX2 inhibitor, on some T cell-related parameters.
MATERIALS AND METHODS
Breast cancer (BC) was induced in BALB/c mice, and then they received DC vaccine treated with lipopolysaccharide (LPS-mDCs), LPS with a 5 μM dose of CXB (LPS/CXB5-mDCs) and LPS with a 10 μM dose of CXB (LPS/CXB10-mDCs). The frequency of splenic Th1 and Treg cells and amounts of IFN-γ, IL-12 and TGF-β production by splenocytes, as well as, the expression of Granzyme-B, T-bet and FOXP3 in tumors were determined using flow cytometry, ELISA, and real-time PCR, respectively.
RESULTS
Compared with untreated tumor group (T-control), treatment with LPS/CXB5-mDCs and LPS/CXB10-mDCs decreased tumor growth (P = 0.009 and P < 0.0001), escalated survival rate (P = 0.002), increased the frequency of splenic Th1 cells (P = 0.0872, and P = 0.0155), increased the IFN-γ (P = 0.0003 and P = 0.0061) and IL-12 (P = 0.001 and P = 0.0009) production by splenocytes, upregulated T-bet (P = 0.062 and P < 0.0001) and Granzyme-B (P = 0.0448 and P = 0.4485), whereas decreased the number of Treg cells (P = 0.0014, and P = 0.0219), reduced the amounts of TGF-β production by splenocytes (P = 0.0535 and P = 0.0169), and reduced the expression of FOXP3 (P = 0.0006 and P = 0.0057) in comparison with T-control group.
CONCLUSIONS
Our findings show that LPS/CXB-treated DC vaccine potently modulated antitumor immune responses in a mouse BC model.
论文信息
- 作者
- Zandvakili R、Basirjafar P、Masoumi J、Zainodini N、Taghipour Z、Khorramdelazad H、Yousefi S、Tavakoli T
- 第一作者单位
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.Iran
- 通讯作者单位
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: Jafarzadeh14@yahoo.com.Iran
- 期刊
- Advances in medical sciences2023 Mar
- 原文标识
- PubMed 37003235 · DOI 10.1016/j.advms.2023.03.002