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The complexity of NK cell origin and feeder cell cues impacts the heterogeneity of expanded NK (eNK) cells. To explore this, we compared the phenotype and function of peripheral blood\u2010derived NK (PB\u2010NK) and umbilical cord blood\u2010derived NK (UCB\u2010NK) cells activated by common feeder cell lines, including K562, PLH, and 221.AEH. After first encounter, most PB\u2010NK cells showed degranulation independently of cytokines production. Meanwhile, most UCB\u2010NK cells did both. We observed that each feeder cell line uniquely influenced the activation, expansion, and ultimate fate of PB eNK and UCB eNK cells, determining whether they became cytokine producers or killer cells. In addition, they also affected the functional performance of NK cell subsets after expansion, that is, expanded conventional NK (ecNK) and expanded FcR\u03b3<jats:sup>\u2013<\/jats:sup> NK (eg\u2010NK)\u00a0cells. Hence, the regulation of eNK cell function largely depends on the NK cell source and the chosen expansion system. These results underscore the significance of selecting feeder cells for NK cell expansion from various sources, notably for customized adoptive cell therapies to yield cytokine\u2010producing or cytotoxic eNK cells.<\/jats:p>","DOI":"10.1002\/mco2.740","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T08:04:11Z","timestamp":1727078651000},"source":"Crossref","is-referenced-by-count":5,"title":["Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4856-0261","authenticated-orcid":false,"given":"Fei","family":"Gao","sequence":"first","affiliation":[{"name":"IRMB University of Montpellier INSERM CHR Montpellier  Montpellier France"},{"name":"Department of Pathology School of Basic Medicine Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio 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