BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors

Felgueres, María-José ; Esteso, Gloria ; García-Jiménez, Álvaro F. ; Dopazo, Ana ; Aguiló, Nacho (Universidad de Zaragoza) ; Mestre-Durán, Carmen ; Martínez-Piñeiro, Luis ; Pérez-Martínez, Antonio ; Reyburn, Hugh T. ; Valés-Gómez, Mar

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41598-024-62968-2

Año: 2024

Publicado en: Scientific reports (Nature Publishing Group) 14, 1 (2024), 16 pp.
ISSN: 2045-2322

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2020-115506RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MCINN/PID2021-123795OB-I00

Tipo y forma: Article (Published version)

Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)