Antibody-dependent cell cytotoxicity synapses form in mice during tumor-specific antibody immunotherapy
| Autor: | André Nicolas, Otto Pritsch, Sophie Viel, Sebastian Amigorena, Pablo Oppezzo, Adele Heitzmann, Xavier Sastre-Garau, Pascale Hubert, Eduardo Osinaga |
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| Přispěvatelé: | Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Département de Biologie des Tumeurs, Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Departamento de inmunobiologia, Facultad de Medicina- Universidad de la República [Montevideo] (UCUR), This work was financially supported by the Institut National de la Sante et de la Recherche Medicale, the Association pour la Recherche sur le Cancer (ARC), the Institut Curie, the EC grant ENCITE, Health-F5-2008-201842, the Institut National du Cancer (INCa)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Institut Curie, Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), INSTITUT CURIE, Réseau International des Instituts Pasteur ( RIIP ) -Institut Pasteur de Montevideo, Universidad de la República-Facultad de Medicina |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Immunological Synapses
Antibodies Neoplasm medicine.medical_treatment MESH : Breast Neoplasms MESH: Neutrophils [ SDV.CAN ] Life Sciences [q-bio]/Cancer MESH: Antibodies Monoclonal MESH : Neutrophils Mice MESH : Antibody-Dependent Cell Cytotoxicity 0302 clinical medicine Antibody Specificity MESH: Animals MESH : Tumor Microenvironment MESH : Receptors IgG MESH : Macrophages Ovarian Neoplasms 0303 health sciences MESH: Antigens Tumor-Associated Carbohydrate Antibodies Monoclonal MESH: Cystadenocarcinoma Serous 3. Good health Oncology 030220 oncology & carcinogenesis Monoclonal MESH: Immunization Passive Antibody MESH: Receptors IgG Monoclonal antibody MESH : Antigens Tumor-Associated Carbohydrate 03 medical and health sciences Antigen In vivo Humans [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology Antineoplastic Agents Alkylating Cyclophosphamide MESH: Humans Macrophages MESH : Humans Antibody-Dependent Cell Cytotoxicity Immunization Passive MESH: Cyclophosphamide Immunotherapy Cystadenocarcinoma Serous MESH: Antibodies Monoclonal Humanized MESH: Female Cancer Research MESH: Combined Modality Therapy MESH : Immunization Passive Neutrophils MESH: Antineoplastic Agents Alkylating MESH: Tumor Microenvironment Tumor Microenvironment MESH : Female MESH : Cyclophosphamide MESH : Immunological Synapses MESH : Antibody Specificity MESH : Cystadenocarcinoma Serous Antibody-dependent cell-mediated cytotoxicity Mice Inbred BALB C biology Combined Modality Therapy MESH: Ovarian Neoplasms MESH : Antibodies Monoclonal Female MESH : Antibodies Neoplasm MESH : Mammary Neoplasms Experimental MESH: Cell Line Tumor medicine.drug_class MESH : Antineoplastic Agents Alkylating MESH: Mammary Neoplasms Experimental MESH: Mice Inbred BALB C Breast Neoplasms chemical and pharmacologic phenomena [SDV.CAN]Life Sciences [q-bio]/Cancer Antibodies Monoclonal Humanized MESH : Antibodies Monoclonal Humanized Cell Line Tumor MESH: Immunological Synapses MESH : Mice medicine MESH: Antibody-Dependent Cell Cytotoxicity Animals Antigens Tumor-Associated Carbohydrate [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Antibody Specificity MESH: Mice MESH : Mice Inbred BALB C 030304 developmental biology Innate immune system MESH : Ovarian Neoplasms MESH : Cell Line Tumor Receptors IgG Mammary Neoplasms Experimental MESH: Macrophages Trastuzumab Molecular biology MESH: Antibodies Neoplasm biology.protein MESH : Animals MESH : Combined Modality Therapy MESH: Breast Neoplasms |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2011, 71 (15), pp.5134-43. ⟨10.1158/0008-5472.CAN-10-4222⟩ Cancer Research; Vol 71 Cancer Research, American Association for Cancer Research, 2011, 71 (15), pp.5134-43. 〈10.1158/0008-5472.CAN-10-4222〉 |
| ISSN: | 0008-5472 1538-7445 |
| DOI: | 10.1158/0008-5472.CAN-10-4222⟩ |
| Popis: | Antibody-dependent cell cytotoxicity (ADCC) plays a critical role in monoclonal antibody (mAb)-mediated cancer therapy. ADCC, however, has not been directly shown in vivo but inferred from the requirement for IgG Fc receptors (FcγR) in tumor rejection in mice. Here, we investigated the mechanism of action of a Tn antigen-specific chimeric mAb (Chi-Tn), which binds selectively to a wide variety of carcinomas, but not to normal tissues, in both humans and mice. Chi-Tn mAb showed no direct toxicity against carcinomas cell lines in vitro but induced the rejection of a murine breast tumor in 80% to 100% of immunocompetent mice, when associated with cyclophosphamide. Tumor rejection was abolished in Fc receptors–associated γ chain (FcR-γ)–deficient mice, suggesting a role for ADCC. Indeed, tumor cells formed stable conjugates in vivo with FcR-γ chain-expressing macrophages and neutrophils in Chi-Tn mAb-treated but not in control mAb-treated mice. The contact zone between tumor cells and ADCC effectors accumulated actin, FcγR and phospho-tyrosines. The in vivo formed ADCC synapses were organized in multifocal supra-molecular activation clusters. These results show that in vivo ADCC mediated by macrophages and neutrophils during tumor rejection by Chi-Tn mAb involves a novel type of multifocal immune synapse between effectors of innate immunity and tumor cells. Cancer Res; 71(15); 5134–43. ©2011 AACR. |
| Databáze: | OpenAIRE |
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