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Interplay between Natural killer cells and Anti-HER2 antibodies: Perspectives for breast cancer immunotherapy

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dc.contributor.author Muntasell i Castellví, Aura, 1972-
dc.contributor.author Cabo, Mariona, 1991-
dc.contributor.author Servitja Tormo, Sonia
dc.contributor.author Tusquets Trias de Bes, Ignacio
dc.contributor.author Martínez-García, Maria
dc.contributor.author Rovira Guerín, Ana
dc.contributor.author Rojo, Federico
dc.contributor.author Albanell Mestres, Joan
dc.contributor.author López-Botet, Miguel
dc.date.accessioned 2018-03-08T09:17:50Z
dc.date.available 2018-03-08T09:17:50Z
dc.date.issued 2017
dc.identifier.citation Muntasell A, Cabo M, Servitja S, Tusquets I, Martínez-García M, Rovira A et al. Interplay between Natural killer cells and Anti-HER2 antibodies: Perspectives for breast cancer immunotherapy. Front Immunol. 2017 Nov 13;8:1544. DOI: 10.3389/fimmu.2017.01544
dc.identifier.issn 1664-3224
dc.identifier.uri http://hdl.handle.net/10230/34067
dc.description.abstract Overexpression of the human epidermal growth factor receptor 2 (HER2) defines a subgroup of breast tumors with aggressive behavior. The addition of HER2-targeted antibodies (i.e., trastuzumab, pertuzumab) to chemotherapy significantly improves relapse-free and overall survival in patients with early-stage and advanced disease. Nonetheless, considerable proportions of patients develop resistance to treatment, highlighting the need for additional and co-adjuvant therapeutic strategies. HER2-specific antibodies can trigger natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity and indirectly enhance the development of tumor-specific T cell immunity; both mechanisms contributing to their antitumor efficacy in preclinical models. Antibody-dependent NK cell activation results in the release of cytotoxic granules as well as the secretion of pro-inflammatory cytokines (i.e., IFNγ and TNFα) and chemokines. Hence, NK cell tumor suppressive functions include direct cytolytic killing of tumor cells as well as the regulation of subsequent antitumor adaptive immunity. Albeit tumors with gene expression signatures associated to the presence of cytotoxic lymphocyte infiltrates benefit from trastuzumab-based treatment, NK cell-related biomarkers of response/resistance to HER2-specific therapeutic antibodies in breast cancer patients remain elusive. Several variables, including (i) the configuration of the patient NK cell repertoire; (ii) tumor molecular features (i.e., estrogen receptor expression); (iii) concomitant therapeutic regimens (i.e., chemotherapeutic agents, tyrosine kinase inhibitors); and (iv) evasion mechanisms developed by progressive breast tumors, have been shown to quantitatively and qualitatively influence antibody-triggered NK cell responses. In this review, we discuss possible interventions for restoring/enhancing the therapeutic activity of HER2 therapeutic antibodies by harnessing NK cell antitumor potential through combinatorial approaches, including immune checkpoint blocking/stimulatory antibodies, cytokines and toll-like receptor agonists.
dc.description.sponsorship The authors are supported by coordinated research projects from Fundación Española contra el Cáncer (GCB15152947MELE) and Proyecto Integrado de Excelencia ISCIII (PIE 2015/00008); ML-B and AM are supported by Worldwide Cancer Research Foundation (15-1146); ML-B by Plan Estatal I + D Retos (SAF2013-49063-C2-1-R; SAF2016-80363-C2-1-R), Spanish Ministry of Economy and Competitiveness (MINECO, FEDER); JA is supported by ISCiii/FEDER (PI15/00146 and CIBERONC) and by Generalitat de Catalunya (2014 SGR 740).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Frontiers in Immunology. 2017 Nov 13;8:1544
dc.rights © 2017 Muntasell, Cabo, Servitja, Tusquets, Martínez-García, Rovira, Rojo, Albanell and López-Botet. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Interplay between Natural killer cells and Anti-HER2 antibodies: Perspectives for breast cancer immunotherapy
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2017.01544
dc.subject.keyword Natural killer cells
dc.subject.keyword Breast cancer
dc.subject.keyword Human epidermal growth factor receptor 2
dc.subject.keyword Trastuzumab
dc.subject.keyword Pertuzumab
dc.subject.keyword Antibody-dependent cell-mediated cytotoxicity
dc.subject.keyword Immunotherapy
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-49063-C2-1-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80363-C2-1-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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