Gut epithelial Interleukin-17 receptor A signaling can modulate distant tumors growth through microbial regulation

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dc.catalogadorgjm
dc.contributor.authorChandra, Vidhi
dc.contributor.authorLi, Le
dc.contributor.authorLe Roux, Olivereen
dc.contributor.authorZhang, Yu
dc.contributor.authorHowell, Rian M.
dc.contributor.authorRupani, Dhwani N.
dc.contributor.authorBaydogan, Seyda
dc.contributor.authorMiller, Haiyan D.
dc.contributor.authorRiquelme Sánchez, Erick Marcelo
dc.contributor.authorPetrosino, Joseph
dc.contributor.authorKim, Michael P.
dc.contributor.authorBhat, Krishna P. L.
dc.contributor.authorWhite, James R.
dc.contributor.authorKolls, Jay K.
dc.contributor.authorPylayeva-Gupta, Yuliya
dc.contributor.authorMcAllister, Florencia
dc.date.accessioned2024-07-19T14:21:24Z
dc.date.available2024-07-19T14:21:24Z
dc.date.issued2024
dc.description.abstractMicrobes influence cancer initiation, progression and therapy responsiveness. IL -17 signaling contributes to gut barrier immunity by regulating microbes but also drives tumor growth. A knowledge gap remains regarding the influence of enteric IL-17-IL-17RA signaling and their microbial regulation on the behavior of distant tumors. We demonstrate that gut dysbiosis induced by systemic or gut epithelial deletion of IL17RA induces growth of pancreatic and brain tumors due to excessive development of Th17, primary source of IL -17 in human and mouse pancreatic ductal adenocarcinoma, as well as B cells that circulate to distant tumors. Microbial dependent IL -17 signaling increases DUOX2 signaling in tumor cells. Inefficacy of pharmacological inhibition of IL-17RA is overcome with targeted microbial ablation that blocks the compensatory loop. These findings demonstrate the complexities of IL-17-IL-17RA signaling in different compartments and the relevance for accounting for its homeostatic host defense function during cancer therapy.
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.ccell.2023.12.006
dc.identifier.eissn1878-3686
dc.identifier.issn1535-6108
dc.identifier.urihttps://doi.org/10.1016/j.ccell.2023.12.006
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87169
dc.identifier.wosidWOS:001154578600001
dc.information.autorucEscuela de Medicina; Riquelme Sánchez, Erick Marcelo; 0000-0002-2696-7995; 1001194
dc.issue.numero1
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final100.e6
dc.pagina.inicio85
dc.revistaCancer Cell
dc.rightsacceso restringido
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGut epithelial Interleukin-17 receptor A signaling can modulate distant tumors growth through microbial regulation
dc.typeartículo
dc.volumen42
sipa.codpersvinculados1001194
sipa.trazabilidadORCID;2024-07-15
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