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Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56<jats:sup>high<\/jats:sup>CD16<jats:sup>+<\/jats:sup>), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with <jats:italic>Bacillus Calmette-Gu\u00e9rin<\/jats:italic> (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D. Strikingly, a NKG2C<jats:sup>+<\/jats:sup>CD57<jats:sup>-<\/jats:sup>Fc\u03b5RI\u03b3<jats:sup>+<\/jats:sup> NK cell population expands after BCG and cytokine stimulation, independently of HCMV serology. This strategy was exploited to rescue anti-tumour NK cells even from the suppressor environment of cancer patients\u2019 bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells.<\/jats:p>","DOI":"10.1038\/s41598-024-62968-2","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T12:02:22Z","timestamp":1717761742000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors"],"prefix":"10.1038","volume":"14","author":[{"given":"Mar\u00eda-Jos\u00e9","family":"Felgueres","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Esteso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro F.","family":"Garc\u00eda-Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Dopazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nacho","family":"Aguil\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mestre-Dur\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Mart\u00ednez-Pi\u00f1eiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"P\u00e9rez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh T.","family":"Reyburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Val\u00e9s-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"62968_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41571-020-0426-7","volume":"18","author":"JA Myers","year":"2021","unstructured":"Myers, J. 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