Neutrophils mediate antibody-induced antitumor effects in mice
Autor: | James P. Di Santo, Pierre Bruhns, Laurence Fiette, Friederike Jönsson, David A. Mancardi, Clifford A. Lowell, Bruno Iannascoli, Marcello Albanesi |
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Přispěvatelé: | Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Immunité Innée, University of California [San Francisco] (UCSF), University of California, This work was supported by the Institut Pasteur and the Institut National de la Santé et de la Recherche Médicale, by Agence Nationale de la Recherche (grant ANR-09-GENO-014-01), Fondation ARC pour la Recherche sur le Cancer and Ligue Nationale contre le Cancer (Comité de Paris) grants (P.B.), through an 'Equipe Labellisée Ligue Contre le Cancer' grant (J.P.D.S.), and by National Institutes of Health, National Institute of Allergy and Infectious Diseases grants AI065495 and AI068150 (C.A.L.)., The authors are thankful to our colleagues at Institut Pasteur (Paris, France): P. Bousso (Dynamics of Immune Responses Unit) for discussions and advice, M.-A. Nicola (Plate-Forme d'Imagerie Dynamique) for help with bioluminescence experiments, X. Montagutelli, Q. Mille, D. Montean, and G. Labas for help with mouse colony management (Central Animal Facility), C. Detchepare and C. Nizak for administrative help (Laboratoire Anticorps en Thérapie et Pathologie), and at University of California, San Francisco (San Francisco, CA): Y. Hu for animal husbandry. The authors are grateful to their colleagues for providing mice or reagents: R. Coffman (DNAX, Palo Alto, CA), B. Hann (University of California, San Francisco), J. J. Lee (Mayo Clinic, Scottsdale, AZ), H. Karasuyama (Tokyo Medical and Dental University Graduate School, Tokyo, Japan), M.P. Reilly (Jefferson Medical College, Philadelphia, PA), and M. Tarik (Montreal University, Montreal, QC, Canada)., ANR-09-GENO-0014,InflammAbs,Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité.(2009), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), University of California [San Francisco] (UC San Francisco), University of California (UC), Martin, Marie, Physiopathologie moléculaire: des maladies rares aux maladies communes - Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité. - - InflammAbs2009 - ANR-09-GENO-0014 - GENO - VALID |
Rok vydání: | 2013 |
Předmět: |
MESH: Tumor Burden
Neutrophils medicine.medical_treatment Melanoma Experimental MESH: Neutrophils MESH: Mice Knockout Biochemistry Immunoglobulin G MESH: Antibodies Monoclonal Antibodies Monoclonal Murine-Derived Mice 0302 clinical medicine Conditional gene knockout MESH: Animals MESH: Trastuzumab Mice Knockout 0303 health sciences biology Melanoma Antibodies Monoclonal Hematology Tumor Burden 3. Good health MESH: Melanoma Experimental 030220 oncology & carcinogenesis [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: Rituximab [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy Antibody Rituximab MESH: Xenograft Model Antitumor Assays MESH: Cell Line Tumor [SDV.IMM] Life Sciences [q-bio]/Immunology MESH: Mice Transgenic medicine.drug_class Immunology Mice Nude Breast Neoplasms Mice Transgenic MESH: Receptors IgG Antibodies Monoclonal Humanized Monoclonal antibody 03 medical and health sciences Antigen MESH: Mice Inbred C57BL Cell Line Tumor MESH: Mice Nude MESH: Antibody-Dependent Cell Cytotoxicity medicine Animals Humans MESH: Mice 030304 developmental biology MESH: Humans Receptors IgG Antibody-Dependent Cell Cytotoxicity Cancer [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy Cell Biology Immunotherapy Trastuzumab medicine.disease Xenograft Model Antitumor Assays Mice Inbred C57BL MESH: Antibodies Monoclonal Humanized MESH: Antibodies Monoclonal Murine-Derived biology.protein MESH: Breast Neoplasms |
Zdroj: | Blood Blood, American Society of Hematology, 2013, 122 (18), pp.3160-3164. ⟨10.1182/blood-2013-04-497446⟩ Blood, 2013, 122 (18), pp.3160-3164. ⟨10.1182/blood-2013-04-497446⟩ |
ISSN: | 1528-0020 0006-4971 |
Popis: | International audience; 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. |
Databáze: | OpenAIRE |
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