Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2024 Oct 17;51(1):1058. doi: 10.1007/s11033-024-10007-8.
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.
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.
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.
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.
与其他乳腺癌亚型相比，三阴性乳腺癌（TNBC）的存活率较低。利用树突状细胞（DC）疫苗作为一种免疫疗法正成为癌症治疗的一种有前途的新方法。然而，肿瘤抗原的免疫原性不足导致 DC 疫苗的效果不尽如人意。外泌体是肿瘤免疫治疗最新进展的基础。本研究探讨了 TNBC 来源的外泌体是否能引发单核细胞来源的树突状细胞（moDC）的成熟和功能的免疫原性，以及外泌体处理的 moDC 对 T 细胞分化的影响。
从 MDA-MB-231 TNBC 癌细胞中分离外泌体并进行鉴定。从外周血单核细胞中分离单核细胞并分化为 DC。然后，用 TNBC 来源的外泌体处理单核细胞来源的 DC。此外，通过 qRT-PCR 和 ELISA 检测试剂盒检测与 DC 成熟和功能相关的基因和细胞因子的 mRNA 水平。我们还将 TNBC 来源的外泌体处理的 moDC 与 T 细胞共培养，并通过 qRT-PCR 评估治疗对 T 细胞分化的作用来研究该处理在 T 细胞分化中的作用。通过 ELISA 检测试剂盒定量检测与外泌体处理的 moDC 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 来源的外泌体通过增强 moDC 的成熟和功能来诱导免疫原性。此外，外泌体处理的 moDC 通过增加细胞因子的产生来促进 TH1 分化，从而促进共培养的 T 细胞的扩增。
TNBC 来源的外泌体可以通过诱导免疫反应和增强 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。
