title: Neutrophils mediate antibody-induced antitumor effects in mice.
abstract: Tumor engraftment followed by monoclonal antibody (mAb) therapy targeting tumor antigens represents a gold standard for assessing the efficiency of mAbs to eliminate tumor cells. Mouse models have demonstrated that receptors for the Fc portion of immunoglobulin G (FcγRs) are critical determinants of mAb therapeutic efficacy, but the FcγR-expressing cell populations responsible remain elusive. We show that neutrophils are responsible for mAb-induced therapy of both subcutaneous syngeneic melanoma and human breast cancer xenografts. mAb-induced tumor reduction, abolished in neutropenic mice, could be restored in FcγR-deficient hosts upon transfer of FcγR+ neutrophils or upon human FcγRIIA/CD32A transgenic expression. Finally, conditional knockout mice unable to perform FcγR-mediated activation and phagocytosis specifically in neutrophils were resistant to mAb-induced therapy. Our work suggests that neutrophils are necessary and sufficient for mAb-induced therapy of subcutaneous tumors, and represent a new and critical focal point for optimizing mAb-induced immunotherapies that will impact on human cancer treatment.
authors: Département d'Immunologie, Laboratoire Anticorps en Thérapie et Pathologie, Institut Pasteur, Paris, France;
authors: Marcello
authors: M
authors: Albanesi
authors: David A
authors: DA
authors: Mancardi
authors: Friederike
authors: F
authors: Jönsson
authors: Bruno
authors: B
authors: Iannascoli
authors: Laurence
authors: L
authors: Fiette
authors: James P
authors: JP
authors: Di Santo
authors: Clifford A
authors: CA
authors: Lowell
authors: Pierre
authors: P
authors: Bruhns
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000069283:Rituximab; D000068878:Trastuzumab; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D000069283:Rituximab; D000068878:Trastuzumab
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