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Novel antitumor therapeutic strategy using CD4+ T cell-derived extracellular vesicles.

Authors :
Shin, Sanghee
Jung, Inseong
Jung, Dokyung
Kim, Christine Seulki
Kang, Sung-Min
Ryu, Suyeon
Choi, Sung-Jin
Noh, Soojeong
Jeong, Jongwon
Lee, Beom Yong
Park, Jun-Kook
Shin, Jiwon
Cho, Hanchae
Heo, Jong-Ik
Jeong, Youngtae
Choi, Sun Ha
Lee, Shin Yup
Baek, Moon-Chang
Yea, Kyungmoo
Source :
Biomaterials. Oct2022, Vol. 289, pN.PAG-N.PAG. 1p.
Publication Year :
2022

Abstract

Extracellular vesicles (EVs) mediate cell-cell crosstalk by carrying bioactive molecules derived from cells. Recently, immune cell-derived EVs have been reported to regulate key biological functions such as tumor progression. CD4+ T cells orchestrate overall immunity; however, the biological role of their EVs is unclear. This study reveals that EVs derived from CD4+ T cells increase the antitumor response of CD8+ T cells by enhancing their proliferation and activity without affecting regulatory T cells (Tregs). Moreover, EVs derived from interleukin-2 (IL2)-stimulated CD4+ T cells induce a more enhanced antitumor response of CD8+ T cells compared with that of IL2-unstimulated CD4+ T cell-derived EVs. Mechanistically, miR-25-3p, miR-155-5p, miR-215-5p, and miR-375 within CD4+ T cell-derived EVs are responsible for the induction of CD8+ T cell-mediated antitumor responses. In a melanoma mouse model, the EVs potently suppress tumor growth through CD8+ T cell activation. This study demonstrates that the EVs, in addition to IL2, are important mediators between CD4+ and CD8+ T cells. Furthermore, unlike IL2, clinically used as an antitumor agent, CD4+ T cell-derived EVs stimulate CD8+ T cells without activating Tregs. Therefore, CD4+ T cell-derived EVs may provide a novel direction for cancer immunotherapy by inducing a CD8+ T cell-mediated antitumor response. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01429612
Volume :
289
Database :
Academic Search Index
Journal :
Biomaterials
Publication Type :
Academic Journal
Accession number :
159432165
Full Text :
https://doi.org/10.1016/j.biomaterials.2022.121765