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Extracellular vesicle-mediated immunoregulation in cancer

  • Progress in Hematology
  • Immunotherapy: Cancer immunotherapy development: From a different perspective
  • Published:
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Abstract

Extracellular vesicles (EVs) have emerged as immunomodulatory regulators during tumor progression. These small vesicles encapsulate a variety of molecules, including DNA, RNA, and proteins. When EVs come in contact with recipient cells, the EVs transmit various physiological characteristics; for example, proteins on the surface of EVs act as ligands. Immune checkpoint blockade targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has shown promise in a subset of cancer patients. PD-L1 on EVs acts as a key immunomodulator. Suppression of EV secretion enhances the efficacy of immunotherapy using immune checkpoint blockade antibodies. In addition to immune checkpoint blockade therapy, chimeric antigen receptor T (CAR-T) cell therapy has also been used to successfully eliminate cancer cells. Interestingly, CAR-T-cell-derived EVs express CAR on their surface. Compared with CAR-T cells, CAR-expressing EVs do not express PD1, so their antitumor effect cannot be weakened. In this review, we describe the current understanding of EVs in cancer immunity and summarize their crucial roles in immunomodulation.

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  1. Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Tomofumi Yamamoto & Takahiro Ochiya

  2. Laboratory of Integrative Oncology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Tomofumi Yamamoto & Yusuke Yamamoto

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  1. Tomofumi Yamamoto
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Yamamoto, T., Yamamoto, Y. & Ochiya, T. Extracellular vesicle-mediated immunoregulation in cancer. Int J Hematol 117, 640–646 (2023). https://doi.org/10.1007/s12185-022-03436-3

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