000118939 001__ 118939
000118939 005__ 20240319081009.0
000118939 0247_ $$2doi$$a10.1136/jitc-2021-004325
000118939 0248_ $$2sideral$$a130069
000118939 037__ $$aART-2022-130069
000118939 041__ $$aeng
000118939 100__ $$0(orcid)0000-0002-0182-201X$$aMoreo, E.$$uUniversidad de Zaragoza
000118939 245__ $$aNovel intravesical bacterial immunotherapy induces rejection of BCG-unresponsive established bladder tumors
000118939 260__ $$c2022
000118939 5060_ $$aAccess copy available to the general public$$fUnrestricted
000118939 5203_ $$aBackground Intravesical BCG is the gold-standard therapy for non-muscle invasive bladder cancer (NMIBC); however, it still fails in a significant proportion of patients, so improved treatment options are urgently needed.
Methods Here, we compared BCG antitumoral efficacy with another live attenuated mycobacteria, MTBVAC, in an orthotopic mouse model of bladder cancer (BC). We aimed to identify both bacterial and host immunological factors to understand the antitumoral mechanisms behind effective bacterial immunotherapy for BC.
Results We found that the expression of the BCG-absent proteins ESAT6/CFP10 by MTBVAC was determinant in mediating bladder colonization by the bacteria, which correlated with augmented antitumoral efficacy. We further analyzed the mechanism of action of bacterial immunotherapy and found that it critically relied on the adaptive cytotoxic response. MTBVAC enhanced both tumor antigen-specific CD4+ and CD8+ T-cell responses, in a process dependent on stimulation of type 1 conventional dendritic cells. Importantly, improved intravesical bacterial immunotherapy using MBTVAC induced eradication of fully established bladder tumors, both as a monotherapy and specially in combination with the immune checkpoint inhibitor antiprogrammed cell death ligand 1 (anti PD-L1).
Conclusion These results contribute to the understanding of the mechanisms behind successful bacterial immunotherapy against BC and characterize a novel therapeutic approach for BCG-unresponsive NMIBC cases.
000118939 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/RTC-2017-6379-1$$9info:eu-repo/grantAgreement/ES/DGA-FEDER/Construyendo Europa desde Aragón$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-097625-B-100
000118939 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000118939 590__ $$a10.9$$b2022
000118939 592__ $$a3.403$$b2022
000118939 591__ $$aONCOLOGY$$b30 / 241 = 0.124$$c2022$$dQ1$$eT1
000118939 593__ $$aCancer Research$$c2022$$dQ1
000118939 591__ $$aIMMUNOLOGY$$b18 / 161 = 0.112$$c2022$$dQ1$$eT1
000118939 593__ $$aImmunology$$c2022$$dQ1
000118939 593__ $$aPharmacology$$c2022$$dQ1
000118939 593__ $$aMolecular Medicine$$c2022$$dQ1
000118939 593__ $$aOncology$$c2022$$dQ1
000118939 593__ $$aImmunology and Allergy$$c2022$$dQ1
000118939 594__ $$a16.8$$b2022
000118939 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000118939 700__ $$0(orcid)0000-0001-7866-2803$$aUranga, S.$$uUniversidad de Zaragoza
000118939 700__ $$0(orcid)0000-0003-4409-1437$$aPicó, A.$$uUniversidad de Zaragoza
000118939 700__ $$0(orcid)0000-0002-9713-2127$$aGómez, A. B.$$uUniversidad de Zaragoza
000118939 700__ $$aNardelli-Haefliger, D.
000118939 700__ $$aDel Fresno, C.
000118939 700__ $$aMurillo, I.
000118939 700__ $$aPuentes, E.
000118939 700__ $$aRodríguez, E.
000118939 700__ $$aVales-Gómez, M.
000118939 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000118939 700__ $$aSancho, D.
000118939 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza
000118939 700__ $$0(orcid)0000-0001-7897-9173$$aAguilo, N.$$uUniversidad de Zaragoza
000118939 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000118939 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000118939 7102_ $$11011$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cProy. investigación HQA
000118939 773__ $$g10, 7 (2022), e004325 [15 pp.]$$pJ. immunotherap. cancer$$tJournal for immunotherapy of cancer$$x2051-1426
000118939 8564_ $$s4669416$$uhttps://zaguan.unizar.es/record/118939/files/texto_completo.pdf$$yVersión publicada
000118939 8564_ $$s3162859$$uhttps://zaguan.unizar.es/record/118939/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000118939 909CO $$ooai:zaguan.unizar.es:118939$$particulos$$pdriver
000118939 951__ $$a2024-03-18-14:59:37
000118939 980__ $$aARTICLE