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Intravenous immunoglobulin promotes antitumor responses by modulating macrophage polarization.

Angeles Domínguez-Soto 1 Mateo de las Casas-Engel 1 Rafael Bragado 2 José Medina-Echeverz 3 Laura Aragoneses-Fenoll 1 Enrique Martín-Gayo 4 Nico van Rooijen 5 Pedro Berraondo 3 María Toribio 4 María Moro 6 Isabel Cuartero 6 Antonio Castrillo 7, 8 David Sancho 9 Carmen Sánchez-Torres 10 Pierre Bruhns 11 Silvia Sánchez-Ramón 12 Angel Corbí 1
1 CSIC - Centro de Investigaciones Biológicas
2 IIS-FJD - Instituto de Investigación Sanitaria Fundación Jiménez Diaz [Madrid]
3 CIMA - Center for Applied Medical Research [Plamplona]
4 CBMSO - Centro de Biología Molecular Severo Ochoa [Madrid]
5 Department of Molecular Cell Biology [Amsterdam UMC]
VUMC - Vrije Universiteit Medical Centre
6 UCM - Universidad Complutense de Madrid [Madrid]
7 IIBM - Instituto de Investigaciones Biomédicas Alberto Sols [Madrid, Spain]
8 Unidad Asociada de Biomedicina
9 CNIC - Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
10 CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional
11 Anticorps en Thérapie et Pathologie
12 Department of Immunology
Abstract : Intravenous Igs (IVIg) therapy is widely used as an immunomodulatory strategy in inflammatory pathologies and is suggested to promote cancer regression. Because progression of tumors depends on their ability to redirect the polarization state of tumor-associated macrophages (from M1/immunogenic/proinflammatory to M2/anti-inflammatory), we have evaluated whether IVIg limits tumor progression and dissemination through modulation of macrophage polarization. In vitro, IVIg inhibited proinflammatory cytokine production from M1 macrophages and induced a M2-to-M1 polarization switch on human and murine M2 macrophages. In vivo, IVIg modified the polarization of tumor-associated myeloid cells in a Fcεr1γ chain-dependent manner, modulated cytokine blood levels in tumor-bearing animals, and impaired tumor progression via FcγRIII (CD16), FcγRIV, and FcRγ engagement, the latter two effects being macrophage mediated. Therefore, IVIg immunomodulatory activity is dependent on the polarization state of the responding macrophages, and its ability to trigger a M2-to-M1 macrophage polarization switch might be therapeutically useful in cancer, in which proinflammatory or immunogenic functions should be promoted.
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Submitted on : Thursday, March 19, 2020 - 3:01:05 PM
Last modification on : Monday, June 21, 2021 - 1:40:03 PM

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Angeles Domínguez-Soto, Mateo de las Casas-Engel, Rafael Bragado, José Medina-Echeverz, Laura Aragoneses-Fenoll, et al.. Intravenous immunoglobulin promotes antitumor responses by modulating macrophage polarization.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2014, 193 (10), pp.5181-5189. ⟨10.4049/jimmunol.1303375⟩. ⟨pasteur-02512274⟩

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