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Here, we investigated the effects of MM\u2010derived EVs on T cells, focusing on markers of T cell exhaustion. Using activated peripheral blood mononuclear cells from healthy donors, we observed immunosuppressive effects such as upregulated expression of immune checkpoint markers on CD8+ T cells treated with MM\u2010derived EVs. Proteomic analysis identified several proteins, such as IL\u20108, SLC1A5, PIN2, and FSP1, associated with regulation of T cell exhaustion and chronic inflammation. Surprisingly, sphingosine kinase 1 (SPHK1) was enriched in MM cell line\u2010derived EVs, implicating SPHK1\/S1P signaling in the immunosuppressive effect of MM EVs. Thus, MM\u2010derived EVs may promote T cell exhaustion via upregulating the expression of immune checkpoint markers and thereby contribute to the formation of the immune\u2010suppressive milieu of MM, resulting in impaired T cell activity.<\/jats:p>","DOI":"10.1111\/cas.70099","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:24:33Z","timestamp":1746750273000},"page":"1861-1870","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Immunosuppressive Effects of Multiple Myeloma\u2010Derived Extracellular Vesicles Through T Cell Exhaustion"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7730-2531","authenticated-orcid":false,"given":"Shinya","family":"Hagiwara","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences and Medical School  Nagoya 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