{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:38:00Z","timestamp":1793151480198,"version":"4.5.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      The ability to generate natural killer (NK) cells from induced pluripotent stem cells (iPSCs) has given rise to new possibilities for the large-scale production of homogeneous immunotherapeutic cellular products and opened new avenues towards the creation of \u201coff-the-shelf\u201d cancer immunotherapies. However, the differentiation of NK cells from iPSCs remains poorly understood, particularly regarding the ontogenic landscape of iPSC-derived NK (iNK) cells produced\n                      <jats:italic>in vitro<\/jats:italic>\n                      and the influence that the differentiation strategy employed may have on the iNK profile.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate this question, we conducted a comparative analysis of two sets of iNK cells generated from the same iPSC line using two different protocols: (i) a short-term, clinically compatible feeder-free protocol corresponding to primitive hematopoiesis, and (ii) a lymphoid-based protocol representing the definitive hematopoietic step.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>Our work demonstrated that both protocols are capable of producing functional iNK cells. However, the two sets of resulting iNKs exhibited distinct phenotypes and transcriptomic profiles. The lymphoid-based differentiation approach generated iNKs with a more mature and activated profile, which demonstrated higher cytotoxicity against cancer cell lines compared to iNK cells produced under short-term feeder-free conditions suggesting that the differentiation strategy must be considered when designing iNK cell\u2013based adoptive immunotherapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1463736","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:55:46Z","timestamp":1728435346000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Comparative analysis of iPSC-derived NK cells from two differentiation strategies reveals distinct signatures and cytotoxic 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