ORIGINAL RESEARCH article
Front. Immunol.
Sec. Antigen Presenting Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1565696
Dendritic cell-derived exosomes induce monocyte antigen-presentation and immune amplification in neoantigen vaccine therapy
Provisionally accepted
Shinji Morisaki1
Hideya Onishi2*
Takafumi Morisaki2Makoto Kubo2Masayo Umebayashi1Hiroto Tanaka1Norihiro Koya1Shinichiro Nakagawa1Kenta Tsujimura1Sachiko Yoshimura3Poh Yin Yew3Kazuma Kiyotani4Yusuke Nakamura4Masafumi Nakamura2Takehiro Torisu2Takanari Kitazono2
Takashi Morisaki1- 1Fukuoka General Cancer Clinic, Fukuoka, Fukuoka, Japan
- 2Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- 3Cancer Precision Medicine Inc, Kawasaki, Kanagawa, Japan
- 4National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Ôsaka, Japan
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Mature dendritic cells release exosomes; however, the immunological role of exosomes in dendritic cell vaccine therapy remains unclear. We examined the immunogenicity of neoantigen peptidepulsed 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 tumorspecific 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.
Keywords: dexosomes, neoantigen, Neoepitope, dendritic cell, Vaccine, immune amplification
Received: 23 Jan 2025; Accepted: 17 Apr 2025.
Copyright: © 2025 Morisaki, Onishi, Morisaki, Kubo, Umebayashi, Tanaka, Koya, Nakagawa, Tsujimura, Yoshimura, Yew, Kiyotani, Nakamura, Nakamura, Torisu, Kitazono and Morisaki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hideya Onishi, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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