000124051 001__ 124051 000124051 005__ 20240731103320.0 000124051 0247_ $$2doi$$a10.1080/2162402X.2022.2160094 000124051 0248_ $$2sideral$$a132593 000124051 037__ $$aART-2023-132593 000124051 041__ $$aeng 000124051 100__ $$aEsteso, Gloria 000124051 245__ $$aBCG-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> 000124051 260__ $$c2023 000124051 5060_ $$aAccess copy available to the general public$$fUnrestricted 000124051 5203_ $$aBacillus 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. 000124051 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/ 000124051 590__ $$a6.5$$b2023 000124051 592__ $$a2.345$$b2023 000124051 591__ $$aONCOLOGY$$b44 / 322 = 0.137$$c2023$$dQ1$$eT1 000124051 593__ $$aImmunology$$c2023$$dQ1 000124051 591__ $$aIMMUNOLOGY$$b30 / 181 = 0.166$$c2023$$dQ1$$eT1 000124051 593__ $$aOncology$$c2023$$dQ1 000124051 593__ $$aImmunology and Allergy$$c2023$$dQ1 000124051 594__ $$a12.8$$b2023 000124051 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000124051 700__ $$aFelgueres, María José 000124051 700__ $$aGarcía Jiménez, Álvaro F. 000124051 700__ $$aReyburn Valés, Christina 000124051 700__ $$aBenguría, Alberto 000124051 700__ $$aVázquez, Enrique 000124051 700__ $$aReyburn, Hugh T. 000124051 700__ $$0(orcid)0000-0001-7897-9173$$aAguiló, Nacho$$uUniversidad de Zaragoza 000124051 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, Carlos$$uUniversidad de Zaragoza 000124051 700__ $$aPuentes, Eugenia 000124051 700__ $$aMurillo, Ingrid 000124051 700__ $$aRodríguez, Esteban 000124051 700__ $$aValés-Gómez, Mar 000124051 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología 000124051 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología 000124051 773__ $$g12, 1 (2023), 2160094 [16 pp]$$pOncoimmunology$$tOncoImmunology$$x2162-4011 000124051 8564_ $$s5719225$$uhttps://zaguan.unizar.es/record/124051/files/texto_completo.pdf$$yVersión publicada 000124051 8564_ $$s1402103$$uhttps://zaguan.unizar.es/record/124051/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000124051 909CO $$ooai:zaguan.unizar.es:124051$$particulos$$pdriver 000124051 951__ $$a2024-07-31-09:42:34 000124051 980__ $$aARTICLE