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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Melanoma is a highly immunogenic cancer, and immunotherapy is the first-line treatment for patients with advanced disease. However, CD155 overexpression in melanoma has been associated with resistance to immunotherapy. Whether CD155 can be transferred from tumour cells via extracellular vesicles (EVs), and how this transfer affects immune responses in melanoma, remains unclear. To investigate melanoma cell transfer of CD155 in vivo, B16F10-WT and B16F10-CD155KO melanoma cells were subcutaneously injected into CD155\u2212\/\u2212 mice. We show that CD155 is transferred from melanoma cells to several immune cell populations infiltrating the tumour, at least partly through EV secretion and uptake. DNAM-1 expression was significantly reduced on natural killer (NK) cells in B16F10-WT tumours compared with B16F10-CD155KO tumours. We also found that CD155 was enclosed and enriched in different melanoma EV subtypes. Finally, incubation of NK cells with CD155+ melanoma EVs increased cellular CD155 levels and led to downregulation of DNAM-1. In summary, melanoma-derived CD155 is enriched in melanoma EVs and transferred to immune cells, especially NK cells. Moreover, cancer-derived CD155+ EVs increase CD155 expression on NK cells and are associated with reduced DNAM-1 expression.<\/jats:p>","DOI":"10.3390\/ijms27198699","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:09:25Z","timestamp":1790683765000},"page":"8699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intercellular Transfer of CD155 Mediated by Melanoma Extracellular Vesicles Downregulates DNAM-1 Expression on NK Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-9440","authenticated-orcid":false,"given":"Li-Ying","family":"Wu","sequence":"first","affiliation":[{"name":"Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia"},{"name":"School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4001, Australia"},{"name":"JC 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Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Department of Otorhinolaryngology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Bioconvergence Science, Graduate School, CHA University, Seongnam 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"JC STEM Lab of Personalised Cancer Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Department of Otorhinolaryngology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, 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Zhi","family":"Chai","sequence":"additional","affiliation":[{"name":"Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9211-5090","authenticated-orcid":false,"given":"Matthias","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology, Oncology and Immunodeficiency, Justus-Liebig-University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-8067","authenticated-orcid":false,"given":"Yong-Soo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Biosciences and Bioengineering, Bioengineering, Inha University, Incheon 22212, Republic of Korea"},{"name":"Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of 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