IgE re-programs alternatively-activated human macrophages towards pro-inflammatory anti-tumoural states.

Autor:	Pellizzari G; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom., Hoskin C; Department of Informatics, Faculty of Natural and Mathematical Sciences, King's College London, Bush House, London WC2B 4BG, United Kingdom., Crescioli S; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom., Mele S; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom., Gotovina J; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria; Department of Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria., Chiaruttini G; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom., Bianchini R; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria; Department of Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria., Ilieva K; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom; Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King's College London, Guy's Cancer Centre, London, United Kingdom., Bax HJ; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom; School of Cancer & Pharmaceutical Sciences, King's College London, Bermondsey Wing, Guy's Hospital, London SE1 9RT, United Kingdom., Papa S; School of Cancer & Pharmaceutical Sciences, King's College London, Bermondsey Wing, Guy's Hospital, London SE1 9RT, United Kingdom; Guy's and St Thomas' NHS Trust, Department of Medical Oncology, London, United Kingdom., Lacy KE; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom., Jensen-Jarolim E; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria; Department of Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria., Tsoka S; Department of Informatics, Faculty of Natural and Mathematical Sciences, King's College London, Bush House, London WC2B 4BG, United Kingdom., Josephs DH; School of Cancer & Pharmaceutical Sciences, King's College London, Bermondsey Wing, Guy's Hospital, London SE1 9RT, United Kingdom; Guy's and St Thomas' NHS Trust, Department of Medical Oncology, London, United Kingdom., Spicer JF; School of Cancer & Pharmaceutical Sciences, King's College London, Bermondsey Wing, Guy's Hospital, London SE1 9RT, United Kingdom., Karagiannis SN; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom. Electronic address: sophia.karagiannis@kcl.ac.uk.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2019 May; Vol. 43, pp. 67-81. Date of Electronic Publication: 2019 Apr 05.
DOI:	10.1016/j.ebiom.2019.03.080
Abstrakt:	Background: Antibody Fc-driven engagement of macrophages is critical for evoking cellular activation and effector functions and influencing tumour-associated macrophage (TAM) recruitment. We previously reported that IgE class antibodies promote restriction of cancer growth in rodent models associated with significant TAM infiltration. However, the human macrophage-associated IgE-Fc Receptor (FcεR) axis remains unexplored. We investigated the effects of anti-tumour IgE stimulation on human macrophage activation. Methods: Human blood monocyte-differentiated quiescent (M0), classically-(M1) and alternatively-(M2) activated macrophages were crosslinked with IgE and polyclonal antibodies to mimic immune complex formation. We examined surface marker expression, cytokine secretion, protein kinase phosphorylation and gene expression in IgE-stimulated macrophages and IgE antibody-dependent macrophage-mediated cytotoxicity (ADCC) against tumour cells. Findings: A proportion (40%) of M2 and (<20%) M0 and M1 macrophages expressed the high-affinity IgE receptor FcεRI. IgE crosslinking triggered upregulation of co-stimulatory CD80, increased TNFα, IFNγ, IL-1β, IL-12, IL-10, IL-13, CXCL9, CXCL11 and RANTES secretion by M0 and M2 and additionally enhanced MCP-1 by M2 macrophages. IgE-stimulated M1 macrophages retained secretion of pro-inflammatory cytokines. IgE crosslinking enhanced the FcεRI-dependent signalling pathway, including phosphorylation of the Lyn kinase, ERK1/2 and p38 in M2 macrophages and upregulated Lyn gene expression by M1 and M2 macrophages. Anti-tumour IgE engendered ADCC of cancer cells by all macrophage subsets. Interpretation: IgE can engage and re-educate alternatively-activated macrophages towards pro-inflammatory phenotypes and prime all subsets to mediate anti-tumour functions. This points to IgE-mediated cascades with potential to activate immune stroma and may be significant in the clinical development of strategies targeting tumour-resident macrophages. (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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