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Human NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration

dc.rights.licenseopenen_US
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorDOMBLIDES, Charlotte
dc.contributor.authorCRAMPTON, Steven
dc.contributor.authorLIU, Hong
dc.contributor.authorBARTLESON, Juliet M.
dc.contributor.authorNGUYEN, Annie
dc.contributor.authorCHAMPAGNE, Claudia
dc.contributor.authorLANDY, Emily E.
dc.contributor.authorSPIKER, Lindsey
dc.contributor.authorPROFFITT, Christopher
dc.contributor.authorBHATTARAI, Sunil
dc.contributor.authorGRAWE, Anissa P.
dc.contributor.authorVALENZUELA, Matias Fuentealba
dc.contributor.authorLARTIGUE, Lydia
dc.contributor.authorMAHOUCHE, Isabelle
dc.contributor.authorDUPAUL-CHICOINE, Jeremy
dc.contributor.authorNISHIMURA, Kazuho
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorLEFORT, Félix
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorDECRAECKER, Marie
dc.contributor.authorVELASCO, Valérie
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorNETZER, Sonia
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorPITARD, Vincent
dc.contributor.authorROY, Christian
dc.contributor.authorSOUBEYRAN, Isabelle
dc.contributor.authorRACINE, Victor
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorBLANCO, Patrick
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorDÉCHANET-MERVILLE, Julie
dc.contributor.authorSALEH, Maya
dc.contributor.authorCANNA, Scott W.
dc.contributor.authorFURMAN, David
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorFAUSTIN, Benjamin
dc.date.accessioned2025-01-21T11:15:24Z
dc.date.available2025-01-21T11:15:24Z
dc.date.issued2024-04
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/204449
dc.description.abstractEnThe immune system can control cancer progression. However, even though some innate immune sensors of cellular stress are expressed intrinsically in epithelial cells, their potential role in cancer aggressiveness and subsequent overall survival in humans is mainly unknown. Here, we show that nucleotide-binding oligomerization domain–like receptor (NLR) family CARD domain–containing 4 (NLRC4) is downregulated in epithelial tumor cells of patients with colorectal cancer (CRC) by using spatial tissue imaging. Strikingly, only the loss of tumor NLRC4, but not stromal NLRC4, was associated with poor immune infiltration (mainly DCs and CD4+ and CD8+ T cells) and accurately predicted progression to metastatic stage IV and decrease in overall survival. By combining multiomics approaches, we show that restoring NLRC4 expression in human CRC cells triggered a broad inflammasome-independent immune reprogramming consisting of type I interferon (IFN) signaling genes and the release of chemokines and myeloid growth factors involved in the tumor infiltration and activation of DCs and T cells. Consistently, such reprogramming in cancer cells was sufficient to directly induce maturation of human DCs toward a Th1 antitumor immune response through IL-12 production in vitro. In multiple human carcinomas (colorectal, lung, and skin), we confirmed that NLRC4 expression in patient tumors was strongly associated with type I IFN genes, immune infiltrates, and high microsatellite instability. Thus, we shed light on the epithelial innate immune sensor NLRC4 as a therapeutic target to promote an efficient antitumor immune response against the aggressiveness of various carcinomas.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enCancer immunotherapy
dc.subject.enCellular immune response
dc.subject.enImmunology
dc.subject.enInnate immunity
dc.subject.enOncology
dc.title.enHuman NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration
dc.typeArticle de revueen_US
dc.identifier.doi10.1172/JCI166085en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologieen_US
dc.identifier.pubmed38652550en_US
bordeaux.journalJournal of Clinical Investigationen_US
bordeaux.volume134en_US
bordeaux.hal.laboratoriesImmunoConcEpT - UMR 5164en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
dc.rights.ccCC BYen_US
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