AUTHOR=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 

TITLE=Dendritic cell-derived exosomes induce monocyte antigen-presentation and immune amplification in neoantigen vaccine therapy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1565696

DOI=10.3389/fimmu.2025.1565696

ISSN=1664-3224

ABSTRACT=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.