000148916 001__ 148916
000148916 005__ 20250123152145.0
000148916 0247_ $$2doi$$a10.3389/fimmu.2021.622995
000148916 0248_ $$2sideral$$a126487
000148916 037__ $$aART-2021-126487
000148916 041__ $$aeng
000148916 100__ $$aEsteso, G.
000148916 245__ $$aNatural killer anti-tumor activity can be achieved by in vitro incubation with heat-killed BCG
000148916 260__ $$c2021
000148916 5060_ $$aAccess copy available to the general public$$fUnrestricted
000148916 5203_ $$aNatural Killer cell receptors allow this heterogeneous immune population to efficiently fight both tumors and infection, so their use as immunotherapy agents is an active field of research. Cytokine activation, particularly by myeloid cell-derived IL15, can induce potent NK anti-tumor responses. While studying the mechanism of action of intravesical instillations of Bacille Calmette-Guerin (BCG) as therapy for patients with high risk non-muscle invasive bladder cancer, we showed that BCG can activate a cytotoxic CD56(bright) NK cell population which efficiently recognized bladder cancer cells. This pioneer immunotherapy provides an invaluable model to understand the role of different immune populations in tumor elimination. However, during the propagation of BCG worldwide a large number of genetically diverse BCG substrains developed. Here, we investigated the capacity of different BCG substrains to promote NK cell activation and confirmed that they were able to activate lymphocytes. Tice, Connaught and Moreau were the substrains with a stronger NK activation effect as measured by CD56 upregulation. Surprisingly, dead mycobacteria also stimulated PBMC cultures and we further demonstrate here that subcellular fractions of BCG-Tice, in the absence of live mycobacteria, could also induce an NK cell response. Lipids from BCG-Tice, but not from Mycobacterium bovis, stimulated NK cell activation and degranulation, whereas the aqueous fraction of either bacteria did not activate lymphocytes. However, delipidated BCG-Tice bacteria were able to activate effector cells (CD3(+)CD56(+) and NK, CD3(-)CD56(+)). These data demonstrate that different components of mycobacteria can stimulate different immune subpopulations resulting in phenotypes suitable for cancer elimination.
000148916 536__ $$9info:eu-repo/grantAgreement/ES/AEI/RTC2017-6379-1$$9info:eu-repo/grantAgreement/ES/AEI/RTI2018-093569-BI00$$9info:eu-repo/grantAgreement/ES/MCINN/RED2018-102411-T
000148916 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000148916 590__ $$a8.787$$b2021
000148916 591__ $$aIMMUNOLOGY$$b35 / 162 = 0.216$$c2021$$dQ1$$eT1
000148916 592__ $$a2.331$$b2021
000148916 593__ $$aImmunology and Allergy$$c2021$$dQ1
000148916 593__ $$aImmunology$$c2021$$dQ1
000148916 594__ $$a9.8$$b2021
000148916 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000148916 700__ $$0(orcid)0000-0001-7897-9173$$aAguiló, N.$$uUniversidad de Zaragoza
000148916 700__ $$aJulián, E.
000148916 700__ $$aAshiru, O.
000148916 700__ $$aHo, M. M.
000148916 700__ $$0(orcid)0000-0003-2993-5478$$aMartin, C.$$uUniversidad de Zaragoza
000148916 700__ $$aVales-Gomez, M.
000148916 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000148916 773__ $$g12 (2021), 622995 [11 pp.]$$pFront. immunol.$$tFrontiers in Immunology$$x1664-3224
000148916 8564_ $$s3737440$$uhttps://zaguan.unizar.es/record/148916/files/texto_completo.pdf$$yVersión publicada
000148916 8564_ $$s2239086$$uhttps://zaguan.unizar.es/record/148916/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000148916 909CO $$ooai:zaguan.unizar.es:148916$$particulos$$pdriver
000148916 951__ $$a2025-01-23-14:47:02
000148916 980__ $$aARTICLE