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Intravenous Immunoglobulin Promotes Antitumor Responses by Modulating Macrophage Polarization

2014; American Association of Immunologists; Volume: 193; Issue: 10 Linguagem: Inglês

10.4049/jimmunol.1303375

1550-6606

Ángeles Domínguez‐Soto, Mateo de las Casas-Engel, Rafael Bragado, José Medina‐Echeverz, Laura Aragoneses-Fenoll, Enrique Martín‐Gayo, Nico van Rooijen, Pedro Berraondo, Marı́a L. Toribio, Marı́a A. Moro, María Isabel Cuartero, Antonio Castrillo, David Sancho, Carmen Sánchez‐Torres, Pierre Bruhns, Silvia Sánchez‐Ramón, Ángel L. Corbí,

Phagocytosis and Immune Regulation

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.