000135828 001__ 135828
000135828 005__ 20240619140701.0
000135828 0247_ $$2doi$$a10.1038/s41598-024-62968-2
000135828 0248_ $$2sideral$$a138843
000135828 037__ $$aART-2024-138843
000135828 041__ $$aeng
000135828 100__ $$aFelgueres, María-José
000135828 245__ $$aBCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors
000135828 260__ $$c2024
000135828 5060_ $$aAccess copy available to the general public$$fUnrestricted
000135828 5203_ $$aThe 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.
000135828 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2020-115506RB-I00$$9info:eu-repo/grantAgreement/ES/MCINN/PID2021-123795OB-I00
000135828 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000135828 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000135828 700__ $$aEsteso, Gloria
000135828 700__ $$aGarcía-Jiménez, Álvaro F.
000135828 700__ $$aDopazo, Ana
000135828 700__ $$0(orcid)0000-0001-7897-9173$$aAguiló, Nacho$$uUniversidad de Zaragoza
000135828 700__ $$aMestre-Durán, Carmen
000135828 700__ $$aMartínez-Piñeiro, Luis
000135828 700__ $$aPérez-Martínez, Antonio
000135828 700__ $$aReyburn, Hugh T.
000135828 700__ $$aValés-Gómez, Mar
000135828 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000135828 773__ $$g14, 1 (2024), 16 pp.$$pSci. rep. (Nat. Publ. Group)$$tScientific reports (Nature Publishing Group)$$x2045-2322
000135828 8564_ $$s7931648$$uhttps://zaguan.unizar.es/record/135828/files/texto_completo.pdf$$yVersión publicada
000135828 8564_ $$s2416522$$uhttps://zaguan.unizar.es/record/135828/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000135828 909CO $$ooai:zaguan.unizar.es:135828$$particulos$$pdriver
000135828 951__ $$a2024-06-19-13:22:38
000135828 980__ $$aARTICLE