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

Novel antitumor therapeutic strategy using CD4+ T cell-derived extracellular vesicles
Shin, S.Jung, I.Jung, D.Kim, C.S.Kang, S.-M.Ryu, S.Choi, S.-J.Noh, S.Jeong, J.Lee, B.Y.Park, J.-K.Shin, J.Cho, H.Heo, J.-I.Jeong, Y.Choi, S.H.Lee, S.Y.Baek, M.-C.Yea, K.
Issued Date
Biomaterials, v.289
Author Keywords
Cancer immunotherapyCD4+ T cellsCD8+ T cellsExtracellular vesiclesInterleukin-2
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. © 2022 Elsevier Ltd
Elsevier Ltd
Related Researcher
  • 정영태 Jeong, Youngtae 뉴바이올로지학과
  • Research Interests Stem cells; Cancer; Precision medicine; Regenerative medicine; Nrf2; antioxidant
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Appears in Collections:
Department of New Biology Lab of Stem Cell Biology & Cancer Precision Medicine 1. Journal Articles
Department of New Biology Protein Engineering Lab 1. Journal Articles


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