135828 20260217205544.0 doi 10.1038/s41598-024-62968-2 sideral 138843 ART-2024-138843 eng Felgueres, María-José BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors 2024 Access copy available to the general public Unrestricted The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56highCD16+), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (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+CD57-FcεRIγ+ 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’ bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells. info:eu-repo/grantAgreement/ES/AEI/PID2020-115506RB-I00 info:eu-repo/grantAgreement/ES/MCINN/PID2021-123795OB-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 3.9 2024 MULTIDISCIPLINARY SCIENCES 25 / 136 = 0.184 2024 Q1 T1 0.874 2024 Multidisciplinary 2024 Q1 6.7 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Esteso, Gloria García-Jiménez, Álvaro F. Dopazo, Ana Aguiló, Nacho Universidad de Zaragoza (orcid)0000-0001-7897-9173 Mestre-Durán, Carmen Martínez-Piñeiro, Luis Pérez-Martínez, Antonio Reyburn, Hugh T. Valés-Gómez, Mar 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 14, 1 (2024), 16 pp. Sci. rep. (Nat. Publ. Group) Scientific reports (Nature Publishing Group) 2045-2322 7931648 http://zaguan.unizar.es/record/135828/files/texto_completo.pdf Versión publicada 2416522 http://zaguan.unizar.es/record/135828/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:135828 articulos driver 2026-02-17-20:37:42 ARTICLE