BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and ¿d T-cells that can be further expanded <i>in vitro</i>

Esteso, Gloria ; Felgueres, María José ; García Jiménez, Álvaro F. ; Reyburn Valés, Christina ; Benguría, Alberto ; Vázquez, Enrique ; Reyburn, Hugh T. ; Aguiló, Nacho (Universidad de Zaragoza) ; Martín, Carlos (Universidad de Zaragoza) ; Puentes, Eugenia ; Murillo, Ingrid ; Rodríguez, Esteban ; Valés-Gómez, Mar

Resumen: Bacillus Calmette-Guérin (BCG), the nonpathogenic Mycobacterium bovis strain used as tuberculosis vaccine, has been successfully used as treatment for non-muscle invasive bladder cancer for decades, and suggested to potentiate cellular and humoral immune responses. However, the exact mechanism of action is not fully understood. We previously described that BCG mainly activated anti-tumor cytotoxic NK cells with upregulation of CD56 and a CD16+ phenotype. Now, we show that stimulation of human peripheral blood mononuclear cells with iBCG, a preparation based on BCG-Moreau, expands oligoclonal γδ T-cells, with a cytotoxic phenotype, together with anti-tumor CD56high CD16+ NK cells. We have used scRNA-seq, flow cytometry, and functional assays to characterize these BCG-activated γδ T-cells in detail. They had a high IFNγ secretion signature with expression of CD27+ and formed conjugates with bladder cancer cells. BCG-activated γδ T-cells proliferated strongly in response to minimal doses of cytokines and had anti-tumor functions, although not fully based on degranulation. BCG was sufficient to stimulate proliferation of γδ T-cells when cultured with other PBMC; however, BCG alone did not stimulate expansion of purified γδ T-cells. The characterization of these non-donor restricted lymphocyte populations, which can be expanded in vitro, could provide a new approach to prepare cell-based immunotherapy tools.

Idioma: Inglés

DOI: 10.1080/2162402X.2022.2160094

Año: 2023

Publicado en: OncoImmunology 12, 1 (2023), 2160094 [16 pp]
ISSN: 2162-4011

Factor impacto JCR: 6.5 (2023)

Categ. JCR: ONCOLOGY rank: 45 / 322 = 0.14 (2023) - Q1 - T1
Categ. JCR: IMMUNOLOGY rank: 31 / 181 = 0.171 (2023) - Q1 - T1

Factor impacto CITESCORE: 12.8 - Immunology and Allergy (Q1) - Oncology (Q1) - Immunology (Q1)

Factor impacto SCIMAGO: 2.345 - Immunology (Q1) - Oncology (Q1) - Immunology and Allergy (Q1)

Tipo y forma: Article (Published version)

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