| dc.rights.license | open | en_US |
| dc.contributor.author | PREILLON, Julie | |
| dc.contributor.author | CUENDE, Julia | |
| dc.contributor.author | RABOLLI, Virginie | |
| dc.contributor.author | GARNERO, Lucile | |
| dc.contributor.author | MERCIER, Marjorie | |
| dc.contributor.author | WALD, Noemie | |
| hal.structure.identifier | Immunology from Concept and Experiments to Translation [ImmunoConcept] | |
| dc.contributor.author | PAPPALARDO, Angela | |
| dc.contributor.author | DENIES, Sofie | |
| dc.contributor.author | JAMART, Diane | |
| dc.contributor.author | MICHAUX, Anne-Catherine | |
| dc.contributor.author | PIRSON, Romain | |
| hal.structure.identifier | Immunology from Concept and Experiments to Translation [ImmunoConcept] | |
| dc.contributor.author | PITARD, Vincent | |
| dc.contributor.author | BAGOT, Martine | |
| dc.contributor.author | PRASAD, Shruthi | |
| dc.contributor.author | HOUTHUYS, Erica | |
| dc.contributor.author | BROUWER, Margreet | |
| dc.contributor.author | MARILLIER, Reece | |
| dc.contributor.author | LAMBOLEZ, Florence | |
| dc.contributor.author | MARCHANTE, Joao R. | |
| dc.contributor.author | NYAWOUAME, Florence | |
| dc.contributor.author | CARTER, Mathew J. | |
| dc.contributor.author | BARON-BODO, Veronique | |
| dc.contributor.author | MARIE-CARDINE, Anne | |
| dc.contributor.author | CRAGG, Mark | |
| hal.structure.identifier | Immunology from Concept and Experiments to Translation [ImmunoConcept] | |
| dc.contributor.author | DECHANET-MERVILLE, Julie | |
| dc.contributor.author | DRIESSENS, Gregory | |
| dc.contributor.author | HOOFD, Catherine | |
| dc.date.accessioned | 2022-10-11T13:37:37Z | |
| dc.date.available | 2022-10-11T13:37:37Z | |
| dc.date.created | 2020-12-04 | |
| dc.date.issued | 2020-12-04 | |
| dc.identifier.issn | 1535-7163 (Print) 1538-8514 (Electronic) 1535-7163 (Linking) | en_US |
| dc.identifier.other | http://mct.aacrjournals.org/content/suppl/2021/01/09/1535-7163.MCT-20-0464.DC1 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/148380 | |
| dc.description.abstractEn | TIGIT 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.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.subject.en | Animals | |
| dc.subject.en | Antibodies : Monoclonal / immunology | |
| dc.subject.en | Antibodies : Neoplasm / immunology | |
| dc.subject.en | Antibodies : Neoplasm / pharmacology | |
| dc.subject.en | Antibody-Dependent Cell Cytotoxicity / drug effects | |
| dc.subject.en | Antigens : CD / metabolism | |
| dc.subject.en | Cytotoxicity : Immunologic / drug effects | |
| dc.subject.en | Female | |
| dc.subject.en | Healthy Volunteers | |
| dc.subject.en | Humans | |
| dc.subject.en | Immunoglobulin G / metabolism | |
| dc.subject.en | Lymphocyte Depletion | |
| dc.subject.en | Lymphocytes : Tumor-Infiltrating / drug effects | |
| dc.subject.en | Lymphocytes : Tumor-Infiltrating / immunology | |
| dc.subject.en | Mice : Inbred BALB C | |
| dc.subject.en | Mice : Inbred C57BL | |
| dc.subject.en | Receptors : Antigen : T-Cell : gamma-delta / metabolism | |
| dc.subject.en | Receptors : IgG / metabolism | |
| dc.subject.en | Receptors : Immunologic / antagonists & inhibitors | |
| dc.subject.en | Receptors : Immunologic / metabolism | |
| dc.subject.en | T-Lymphocytes : Regulatory / drug effects | |
| dc.subject.en | T-Lymphocytes : Regulatory / immunology | |
| dc.title.en | Restoration 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.alternative | Mol Cancer Ther | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1158/1535-7163.MCT-20-0464 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Immunologie | en_US |
| dc.identifier.pubmed | 33277440 | en_US |
| bordeaux.journal | Molecular Cancer Therapeutics | en_US |
| bordeaux.page | 121-131 | en_US |
| bordeaux.volume | 20 | en_US |
| bordeaux.hal.laboratories | ImmunoConcEpT - UMR 5164 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.export | false | |
| workflow.import.source | pubmed | |
| dc.rights.cc | CC BY-NC-ND | en_US |
| bordeaux.COinS | ctx_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 | |
