Triple-negative breast cancer-derived exosomes change the immunological features of human monocyte-derived dendritic cells and influence T-cell responses.

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sahar Safaei, Shiva Alipour, Seyedeh Zahra Bahojb Mahdavi, Hooman Shalmashi, Vahid Khaze Shahgoli, Dariush Shanehbandi, Behzad Baradaran, Tohid Kazemi
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引用次数: 0

Abstract

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.

三阴性乳腺癌外泌体改变了人类单核细胞衍生树突状细胞的免疫学特征,并影响了T细胞反应。
背景:三阴性乳腺癌(TNBC与其他乳腺癌亚型相比,三阴性乳腺癌(TNBC)的生存率较低。利用树突状细胞(DC)疫苗作为一种免疫疗法正成为一种前景广阔的癌症治疗新方法。然而,肿瘤抗原的免疫原性不足导致树突状细胞疫苗的效果不尽人意。外泌体是肿瘤免疫疗法取得最新进展的基础。本研究考察了 TNBC 衍生的外泌体是否会对单核细胞衍生 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衍生 DC(moDC)对 T 细胞分化的影响。方法:从 MDA-MB-231 TNBC 癌细胞中分离出外泌体并对其进行鉴定。然后,用 TNBC 衍生的外泌体处理单核细胞衍生的 DC。此外,我们还使用 qRT-PCR 和 ELISA 方法检测了参与 DC 成熟和功能的基因和细胞因子的 mRNA 水平。我们还将经 TNBC 外泌体处理的 moDCs 与 T 细胞进行了共培养,并通过 qRT-PCR 评估了一些相关基因的表达,从而研究了处理在 T 细胞分化中的作用。用ELISA检测法量化了与外泌体处理过的moDCs共培养的T细胞分泌的细胞因子的浓度:我们的研究结果表明,TNBC衍生的外泌体通过增强moDCs的成熟和功能诱导免疫原性。此外,经外泌体处理的moDCs可通过增加细胞因子的产生诱导TH1分化,从而促进共培养T细胞的扩增:结论:TNBC衍生的外泌体可通过诱导免疫原性反应和提高DC疫苗的有效性来改善疫苗诱导的免疫疗法。不过,这还需要在今后的研究中进一步探讨。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Biology Reports
Molecular Biology Reports 生物-生化与分子生物学
CiteScore
5.00
自引率
0.00%
发文量
1048
审稿时长
5.6 months
期刊介绍: Molecular Biology Reports publishes original research papers and review articles that demonstrate novel molecular and cellular findings in both eukaryotes (animals, plants, algae, funghi) and prokaryotes (bacteria and archaea).The journal publishes results of both fundamental and translational research as well as new techniques that advance experimental progress in the field and presents original research papers, short communications and (mini-) reviews.
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