树突状细胞衍生的外泌体在新抗原疫苗治疗中诱导单核细胞抗原呈递和免疫放大。
Dendritic cell-derived exosomes induce monocyte antigen-presentation and immune amplification in neoantigen vaccine therapy.
作者信息
Morisaki Shinji, Onishi Hideya, Morisaki Takafumi, Kubo Makoto, Umebayashi Masayo, Tanaka Hiroto, Koya Norihiro, Nakagawa Shinichiro, Tsujimura Kenta, Yoshimura Sachiko, Yew Poh Yin, Kiyotani Kazuma, Nakamura Yusuke, Nakamura Masafumi, Torisu Takehiro, Kitazono Takanari, Morisaki Takashi
机构信息
Fukuoka General Cancer Clinic, Fukuoka, Japan.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
出版信息
Front Immunol. 2025 May 19;16:1565696. doi: 10.3389/fimmu.2025.1565696. eCollection 2025.
Mature dendritic cells release exosomes; however, the immunological role of exosomes in dendritic cell vaccine therapy remains unclear. We examined the immunogenicity of neoantigen peptide-pulsed dendritic cell-derived exosomes (Neo-P DEX) and investigated their role in vaccine therapy. The quality of DEX derived from dendritic cell cultures was confirmed via electron microscopy, western blotting, flow cytometry, and CD63 ELISA. When DEX released from neoantigen-pulsed DCs was applied to monocytes, they showed dendritic cell-like properties such as surface antigen expression. Furthermore, monocytes receiving Neo-P DEX activated neoantigen-reactive T lymphocytes. Fluorescence-activated cell sorting (FACS) analysis showed that plasma exosomes after neoantigen-pulsed DC vaccine may contain more DEX compared to before the vaccine, suggesting that DEX released after DC vaccination may be involved in the amplification of tumor-specific immune responses by translocating to monocytes in the patient body and transforming them into antigen-presenting dendritic cells. This study suggests that dendritic cell exosomes may act as endogenous neoantigen vaccines or immune amplifiers.
成熟的树突状细胞会释放外泌体;然而,外泌体在树突状细胞疫苗治疗中的免疫作用仍不清楚。我们检测了新抗原肽脉冲树突状细胞衍生外泌体(Neo-P DEX)的免疫原性,并研究了它们在疫苗治疗中的作用。通过电子显微镜、蛋白质印迹、流式细胞术和CD63酶联免疫吸附测定法确认了从树突状细胞培养物中获得的外泌体的质量。当将新抗原脉冲树突状细胞释放的外泌体应用于单核细胞时,它们表现出树突状细胞样特性,如表面抗原表达。此外,接受Neo-P DEX的单核细胞激活了新抗原反应性T淋巴细胞。荧光激活细胞分选(FACS)分析表明,新抗原脉冲树突状细胞疫苗接种后的血浆外泌体可能比接种疫苗前含有更多的外泌体,这表明树突状细胞疫苗接种后释放的外泌体可能通过转移到患者体内的单核细胞并将它们转化为抗原呈递树突状细胞而参与肿瘤特异性免疫反应的放大。这项研究表明,树突状细胞外泌体可能充当内源性新抗原疫苗或免疫放大器。