2026-04-29T02:37:36Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/259002025-12-18T13:01:30Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Felgueres, María-José author Esteso, Gloria author García-Jiménez, Álvaro F author Dopazo, Ana author Aguiló, Nacho author Mestre-Durán, Carmen author Martínez-Piñeiro, Luis author Pérez-Martínez, Antonio author Reyburn, Hugh T author Valés-Gómez, Mar author 2024-06-07 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 (CD56CD16), 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 NKG2CCD57FcεRIγ 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. Sci Rep. 2024 Jun 7;14(1):13133. https://hdl.handle.net/20.500.12105/25900 38849432 BCG Cancer immunology Cell immunotherapy Cytokine activation NK cells BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors.