title: Use of carbosilane dendrimer to switch macrophage polarization for the acquisition of antitumor functions.
abstract: Tumor microenvironment favors the escape from immunosurveillance by promoting immunosuppression and blunting pro-inflammatory responses. Since most tumor-associated macrophages (TAM) exhibit an M2-like tumor cell growth promoting polarization, we have studied the role of 2G-03NN24 carbosilane dendrimer in M2 macrophage polarization to evaluate the potential application of dendrimers in tumor immunotherapy. We found that the 2G-03NN24 dendrimer decreases LPS-induced IL-10 production from in vitro generated monocyte-derived M2 macrophages, and also switches their gene expression profile towards the acquisition of M1 polarization markers (INHBA, SERPINE1, FLT1, EGLN3 and ALDH1A2) and the loss of M2 polarization-associated markers (EMR1, IGF1, FOLR2 and SLC40A1). Furthermore, 2G-03NN24 dendrimer decreases STAT3 activation. Our results indicate that the 2G-03NN24 dendrimer can be a useful tool for antitumor therapy by virtue of its potential ability to limit the M2-like polarization of TAM.
authors.affiliation: Laboratorio Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain. mmunoz.hgugm@gmail.com mmunoz.hgugm@salud.madrid.org.
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Perisé-Barrios
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez
authors.forename: Angel L
authors.initials: AL
authors.lastname: Corbí
authors.forename: Javier
authors.initials: J
authors.lastname: de la Mata
authors.forename: Angeles
authors.initials: A
authors.lastname: Domínguez-Soto
authors.forename: María A
authors.initials: MA
authors.lastname: Muñoz-Fernandez
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007167:Immunotherapy; D016753:Interleukin-10 / Q000378:metabolism; D020014:K562 Cells; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D017646:Organosilicon Compounds / Q000737:chemistry* / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012821:Silanes / Q000737:chemistry*
chemical_list: C000594597:2G-03NN24; D015415:Biomarkers; D050091:Dendrimers; D008070:Lipopolysaccharides; D017646:Organosilicon Compounds; D050796:STAT3 Transcription Factor; D012821:Silanes; C504072:carbosilane; D016753:Interleukin-10