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dc.rights.licenseopenen_US
dc.contributor.authorPREILLON, Julie
dc.contributor.authorCUENDE, Julia
dc.contributor.authorRABOLLI, Virginie
dc.contributor.authorGARNERO, Lucile
dc.contributor.authorMERCIER, Marjorie
dc.contributor.authorWALD, Noemie
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorPAPPALARDO, Angela
dc.contributor.authorDENIES, Sofie
dc.contributor.authorJAMART, Diane
dc.contributor.authorMICHAUX, Anne-Catherine
dc.contributor.authorPIRSON, Romain
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorPITARD, Vincent
dc.contributor.authorBAGOT, Martine
dc.contributor.authorPRASAD, Shruthi
dc.contributor.authorHOUTHUYS, Erica
dc.contributor.authorBROUWER, Margreet
dc.contributor.authorMARILLIER, Reece
dc.contributor.authorLAMBOLEZ, Florence
dc.contributor.authorMARCHANTE, Joao R.
dc.contributor.authorNYAWOUAME, Florence
dc.contributor.authorCARTER, Mathew J.
dc.contributor.authorBARON-BODO, Veronique
dc.contributor.authorMARIE-CARDINE, Anne
dc.contributor.authorCRAGG, Mark
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorDECHANET-MERVILLE, Julie
dc.contributor.authorDRIESSENS, Gregory
dc.contributor.authorHOOFD, Catherine
dc.date.accessioned2022-10-11T13:37:37Z
dc.date.available2022-10-11T13:37:37Z
dc.date.created2020-12-04
dc.date.issued2020-12-04
dc.identifier.issn1535-7163 (Print) 1538-8514 (Electronic) 1535-7163 (Linking)en_US
dc.identifier.otherhttp://mct.aacrjournals.org/content/suppl/2021/01/09/1535-7163.MCT-20-0464.DC1en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/148380
dc.description.abstractEnTIGIT is an immune checkpoint inhibitor expressed by effector CD4þ and CD8þ T cells, NK cells, and regulatory T cells (Tregs). Inhibition of TIGIT-ligand binding using antagonistic anti-TIGIT mAbs has shown in vitro potential to restore T-cell function and therapeutic efficacy in murine tumor models when combined with an anti–PD(L)-1 antibody. In the current work, we demonstrate broader TIGIT expression than previously reported in healthy donors and patients with cancer with expression on gd T cells, particularly in CMV-seropositive donors, and on tumor cells from hematologic malignancies. Quantification of TIGIT density revealed tumor-infiltrating Tregs as the population expressing the highest receptor density. Consequently, the therapeutic potential of anti-TIGIT mAbs might be wider than the previously described anti–PD(L)-1-like restoration of ab T-cell function. CD155 also mediated inhibition of gd T cells, an immune population not previously described to be sensitive to TIGIT inhibition, which could be fully prevented via use of an antagonistic anti-TIGIT mAb (EOS-448). In PBMCs from patients with cancer, as well as in tumor-infiltrating lymphocytes from mice, the higher TIGIT expression in Tregs correlated with strong antibody-dependent killing and preferential depletion of this highly immunosuppressive population. Accordingly, the ADCC/ADCP–enabling format of the anti-TIGIT mAb had superior antitumor activity, which was dependent upon Fcg receptor engagement. In addition, the anti-TIGIT mAb was able to induce direct killing of TIGITexpressing tumor cells both in human patient material and in animal models, providing strong rationale for therapeutic intervention in hematologic malignancies. These findings reveal multiple therapeutic opportunities for anti-TIGIT mAbs in cancer therapeutics.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enAnimals
dc.subject.enAntibodies : Monoclonal / immunology
dc.subject.enAntibodies : Neoplasm / immunology
dc.subject.enAntibodies : Neoplasm / pharmacology
dc.subject.enAntibody-Dependent Cell Cytotoxicity / drug effects
dc.subject.enAntigens : CD / metabolism
dc.subject.enCytotoxicity : Immunologic / drug effects
dc.subject.enFemale
dc.subject.enHealthy Volunteers
dc.subject.enHumans
dc.subject.enImmunoglobulin G / metabolism
dc.subject.enLymphocyte Depletion
dc.subject.enLymphocytes : Tumor-Infiltrating / drug effects
dc.subject.enLymphocytes : Tumor-Infiltrating / immunology
dc.subject.enMice : Inbred BALB C
dc.subject.enMice : Inbred C57BL
dc.subject.enReceptors : Antigen : T-Cell : gamma-delta / metabolism
dc.subject.enReceptors : IgG / metabolism
dc.subject.enReceptors : Immunologic / antagonists & inhibitors
dc.subject.enReceptors : Immunologic / metabolism
dc.subject.enT-Lymphocytes : Regulatory / drug effects
dc.subject.enT-Lymphocytes : Regulatory / immunology
dc.title.enRestoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies
dc.title.alternativeMol Cancer Theren_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1158/1535-7163.MCT-20-0464en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologieen_US
dc.identifier.pubmed33277440en_US
bordeaux.journalMolecular Cancer Therapeuticsen_US
bordeaux.page121-131en_US
bordeaux.volume20en_US
bordeaux.hal.laboratoriesImmunoConcEpT - UMR 5164en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
workflow.import.sourcepubmed
dc.rights.ccCC BY-NC-NDen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Cancer%20Therapeutics&rft.date=2020-12-04&rft.volume=20&rft.issue=1&rft.spage=121-131&rft.epage=121-131&rft.eissn=1535-7163%20(Print)%201538-8514%20(Electronic)%201535-7163%20(Linking)&rft.issn=1535-7163%20(Print)%201538-8514%20(Electronic)%201535-7163%20(Linking)&rft.au=PREILLON,%20Julie&CUENDE,%20Julia&RABOLLI,%20Virginie&GARNERO,%20Lucile&MERCIER,%20Marjorie&rft.genre=article


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