CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
三阴性乳腺癌来源的外泌体改变人单核细胞衍生树突状细胞的免疫学特征并影响 T 细胞反应
英文原题：Triple-negative breast cancer-derived exosomes change the immunological features of human monocyte-derived dendritic cells and influence T-cell responses.
查看英文原题
Triple-negative breast cancer-derived exosomes change the immunological features of human monocyte-derived dendritic cells and influence T-cell responses.
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研究概要
TNBC 来源的外泌体可能通过诱导免疫原性反应并增强 DC 疫苗的有效性来改善疫苗引发的免疫治疗。然而，这需要在未来的研究中进一步探讨。
研究思路结论见上方概要
背景
三阴性乳腺癌（TNBC）相比其他BC亚型表现出较低的生存率。利用树突状细胞（DC）疫苗作为免疫治疗的一种形式，正成为癌症治疗中一种有前景的新方法。然而，肿瘤抗原免疫原性不足导致DC疫苗效果不理想。外泌体是肿瘤免疫治疗最新改进的基础。本研究探讨了TNBC来源的外泌体是否对单核细胞来源DC的成熟和功能产生免疫原性，以及经外泌体处理的单核细胞来源DC（moDCs）对T细胞分化的影响。
方法
外泌体从MDA-MB-231 TNBC癌细胞中分离并表征。单核细胞从外周血单个核细胞中分离并分化为DCs。然后，单核细胞衍生的DCs用TNBC衍生的外泌体处理。此外，使用qRT-PCR和ELISA测定法检测了参与DC成熟和功能的基因和细胞因子的mRNA水平。我们还将TNBC衍生的外泌体处理的moDCs与T细胞共培养，并通过qRT-PCR评估一些相关基因的表达，研究了该处理在T细胞分化中的作用。通过ELISA测定法定量了与经外泌体处理的moDCs共培养的T细胞分泌的细胞因子的浓度。
结果
我们的研究结果表明，TNBC来源的外泌体通过增强moDCs的成熟和功能来诱导免疫原性。此外，经外泌体处理的moDCs通过增加细胞因子产生来诱导TH1分化，从而促进共培养T细胞的扩增。
展开英文摘要原文
BACKGROUND
Triple-negative breast cancer (TNBC) exhibits a lower survival rate in comparison to other BC subtypes. Utilizing dendritic cell (DC) vaccines as a form of immunotherapy is becoming a promising new approach to cancer treatment. However, inadequate immunogenicity of tumor antigens leads to unsatisfactory effectiveness of the DC vaccines. Exosomes are the basis for the latest improvements in tumor immunotherapy. This study examined whether TNBC-derived exosomes elicit immunogenicity on the maturation and function of monocyte-derived DCs and the impact of the exosome-treated monocyte-derived DCs (moDCs) on T cell differentiation.
METHODS
exosomes were isolated from MDA-MB-231 TNBC cancer cells and characterized. Monocytes were separated from peripheral blood mononuclear cells and differentiated into DCs. Then, monocyte-derived DCs were treated with TNBC-derived exosomes. Furthermore, the mRNA levels of the genes and cytokines involved in DC maturation and function were examined using qRT-PCR and ELISA assays. We also cocultured TNBC-derived exosome-treated moDCs with T cells and investigated the role of the treatment in T cell differentiation by evaluating the expression of some related genes by qRT-PCR. The concentration of the cytokines secreted from T cells cocultured with exosome-treated moDCs was quantified by the ELISA assays.
RESULTS
Our findings showed that TNBC-derived exosomes induce immunogenicity by enhancing moDCs' maturation and function. In addition, exosome-treated moDCs promote cocultured T-cell expansion by inducing TH1 differentiation through increasing cytokine production.
CONCLUSION
TNBC-derived exosomes could improve vaccine-elicited immunotherapy by inducing an immunogenic response and enhancing the effectiveness of the DC vaccines. However, this needs to be investigated further in future studies.
论文信息
- 作者
- Safaei S、Alipour S、Bahojb Mahdavi SZ、Shalmashi H、Shahgoli VK、Shanehbandi D、Baradaran B、Kazemi T
- 第一作者单位
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Iran
- 通讯作者单位
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Tohid_kazemi@yahoo.com.Iran
- 期刊
- Molecular biology reports2024 Oct 17
- 原文标识
- PubMed 39417912 · DOI 10.1007/s11033-024-10007-8