000171038 001__ 171038
000171038 005__ 20260505142649.0
000171038 0247_ $$2doi$$a10.1016/j.ccell.2026.02.013
000171038 0248_ $$2sideral$$a149120
000171038 037__ $$aART-2026-149120
000171038 041__ $$aeng
000171038 100__ $$aMarco, Sonia
000171038 245__ $$aRadiotherapy synergizes with an inducible AAV-based immunotherapy platform to program local and systemic antitumor immunity
000171038 260__ $$c2026
000171038 5060_ $$aAccess copy available to the general public$$fUnrestricted
000171038 5203_ $$aRadiotherapy (RT) can prime the immune system against cancer but often fails to generate effective antitumor responses due to concomitant induction of immunosuppressive factors. To overcome this limitation, we built upon the observation that RT enhances adeno-associated vectors (AAVs) tumor transduction through the epigenetic modification of vector episomes. We designed an AAV-based platform to deliver immunostimulatory cytokines through an interferon (IFN)-inducible promoter that allows for spatial control of transgene expression into irradiated tumors. As opposed to a constitutive system, local delivery of a vector encoding for inducible IL-12 (AAV-iIL12) achieves an efficient production of the cytokine without significant toxicity. Combination of RT and AAV-iIL12 generates a highly immunostimulatory tumor microenvironment (TME) leading to robust local and systemic antitumor responses in an IFNγ- and FAS-dependent manner, able to overcome common immune-evasion mechanisms. Our work shows that radiation coupled with AAV-based immune-gene delivery is an efficient and safe approach to treat cancer.
000171038 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B29-20R$$9info:eu-repo/grantAgreement/ES/ISCIII/CB21-13-00087$$9info:eu-repo/grantAgreement/ES/MCIU-AEI/PID2020-113963RB-I00 Desasignar$$9info:eu-repo/grantAgreement/ES/MCIU/PID2024-160227OB-I00
000171038 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000171038 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000171038 700__ $$aFernández, Myriam
000171038 700__ $$aHonorato, Beatriz
000171038 700__ $$aJuanarena, Nerea
000171038 700__ $$aSainz, Cristina
000171038 700__ $$aAndueza, Ainhoa
000171038 700__ $$aGould, David J.
000171038 700__ $$aAnderson, Seth
000171038 700__ $$ade Andrea, Carlos
000171038 700__ $$aDomínguez, Paulo Pérez
000171038 700__ $$aWong, Paolo
000171038 700__ $$aVásquez, Carlos
000171038 700__ $$aNarinda, Irene
000171038 700__ $$aUnzu, Carmen
000171038 700__ $$aIsola, Sergio
000171038 700__ $$aTavira, Beatriz
000171038 700__ $$aAriz, Mikel
000171038 700__ $$aCamps, Gracián
000171038 700__ $$aSanmamed, Miguel F.
000171038 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, Julián$$uUniversidad de Zaragoza
000171038 700__ $$aLabiano, Sara
000171038 700__ $$aAlonso, Marta M.
000171038 700__ $$aMarco-Sanz, Javier
000171038 700__ $$aGuruceaga, Elizabeth
000171038 700__ $$aCollantes, María
000171038 700__ $$aSimón, Jon Ander
000171038 700__ $$aPeñuelas, Iván
000171038 700__ $$aFernández-Irigoyen, Joaquín
000171038 700__ $$aSantamaría, Enrique
000171038 700__ $$aPrieto, Jesús
000171038 700__ $$aDubrot, Juan
000171038 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000171038 773__ $$g44 (2026), 17 pp.$$pCANCER CELL$$tCANCER CELL$$x1535-6108
000171038 8564_ $$s16131738$$uhttps://zaguan.unizar.es/record/171038/files/texto_completo.pdf$$yVersión publicada
000171038 8564_ $$s1781663$$uhttps://zaguan.unizar.es/record/171038/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000171038 909CO $$ooai:zaguan.unizar.es:171038$$particulos$$pdriver
000171038 951__ $$a2026-05-05-13:36:17
000171038 980__ $$aARTICLE