000162956 001__ 162956
000162956 005__ 20251017144637.0
000162956 0247_ $$2doi$$a10.1038/s41417-025-00948-y
000162956 0248_ $$2sideral$$a145473
000162956 037__ $$aART-2025-145473
000162956 041__ $$aeng
000162956 100__ $$0(orcid)0000-0002-7963-7797$$aGuerrero, Claudia
000162956 245__ $$aNK cells mediate preventive efficacy of intravenous BCG against lung metastasis in mice
000162956 260__ $$c2025
000162956 5060_ $$aAccess copy available to the general public$$fUnrestricted
000162956 5203_ $$aLung metastases frequently arise from primary tumors, including bladder cancer, and represent a critical negative prognostic factor. Natural Killer (NK) cells have shown to play a vital role in controlling metastasis. Consequently, tumor cells have evolved specific mechanisms to evade NK cell-mediated immune surveillance, promoting metastasis and resistance to immunotherapy. In this study, we investigated the prophylactic and therapeutic potential of intravenous Bacillus Calmette–Guerin (BCG) in preventing lung metastases from bladder cancer cells using a murine model. We demonstrated that prophylactic BCG administration significantly reduced tumor burden and prolonged survival, largely through NK cell activation. However, BCG treatment was ineffective when administered over established tumors, likely due to tumor-driven immune evasion mechanisms. Our results revealed the contribution of interferon-gamma (IFN-γ) to tumor resistance. Tumor cells exposed to IFN-γ were more resistant to BCG in vivo, which correlated with the overexpression of immune checkpoint molecules, whereas disruption of the IFN-γ signaling pathway in tumor cells partially restored the therapeutic efficacy of BCG. Our findings highlight the importance of understanding tumor immune escape mechanisms and suggest that BCG could be a promising treatment for preventing lung metastases in bladder cancer.
000162956 536__ $$9info:eu-repo/grantAgreement/ES/DGA/LMP50-21$$9info:eu-repo/grantAgreement/ES/ISCIII/CB06-06-0020$$9info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097625-B-I00$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/PRTR-C17.I1$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-138624OB-I00
000162956 540__ $$9info:eu-repo/semantics/embargoedAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000162956 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000162956 700__ $$aCasal, Marta$$uUniversidad de Zaragoza
000162956 700__ $$aAlierta, Cristina$$uUniversidad de Zaragoza
000162956 700__ $$0(orcid)0000-0002-0182-201X$$aMoreo, Eduardo
000162956 700__ $$aAraujo-Voces, Miguel$$uUniversidad de Zaragoza
000162956 700__ $$0(orcid)0000-0001-7866-2803$$aUranga, Santiago$$uUniversidad de Zaragoza
000162956 700__ $$0(orcid)0000-0002-9713-2127$$aGómez, Ana Belén$$uUniversidad de Zaragoza
000162956 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, Carlos$$uUniversidad de Zaragoza
000162956 700__ $$0(orcid)0000-0001-7897-9173$$aAguiló, Nacho$$uUniversidad de Zaragoza
000162956 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000162956 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000162956 7102_ $$11011$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cProy. investigación HQA
000162956 773__ $$g32 (2025), 1090–1097$$pCancer gene ther.$$tCANCER GENE THERAPY$$x0929-1903
000162956 8564_ $$s4667233$$uhttps://zaguan.unizar.es/record/162956/files/texto_completo.pdf$$yPostprint$$zinfo:eu-repo/date/embargoEnd/2026-02-02
000162956 8564_ $$s732776$$uhttps://zaguan.unizar.es/record/162956/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint$$zinfo:eu-repo/date/embargoEnd/2026-02-02
000162956 909CO $$ooai:zaguan.unizar.es:162956$$particulos$$pdriver
000162956 951__ $$a2025-10-17-14:30:07
000162956 980__ $$aARTICLE