Targeted Delivery of α-Galactosylceramide to CD8α + Dendritic Cells Optimizes Type I NKT Cell–Based Antitumor Responses
| العنوان: | Targeted Delivery of α-Galactosylceramide to CD8α + Dendritic Cells Optimizes Type I NKT Cell–Based Antitumor Responses |
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| المؤلفون: | Emilie Bialecki, François Trottein, Luis J. Cruz, Josette Fontaine, Reem Ghinnagow, Elodie Macho-Fernandez, Benoît Frisch, Christelle Faveeuw |
| المساهمون: | Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Leiden University Medical Center (LUMC), Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was supported by INSERM, Centre National de la Recherche Scientifique, University of Lille 2, Pasteur Institute of Lille, and Institut National du Cancer (projets libres) under reference R08046EE/RPT08003EEA., We thank Drs. C. Reis e Sousa (London Research Institute, London, U.K.), L. Van Kaer (Vanderbilt University, Nashville, TN), and A. Bendelac (University of Chicago, Chicago, IL) for the gift of B16F10 melanoma cells expressing OVA, EG7 cells, CD1d−/− C57BL/6 mice, and the NKT cell hybridoma DN32.D3, respectively. We thank the National Institute of Allergy and Infectious Diseases Tetramer Facility (Emory University, Atlanta, GA) for their generous support in supplying CD1d tetramers., TROTTEIN, François, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universiteit Leiden |
| المصدر: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2014, 193 (2), pp.961-969. ⟨10.4049/jimmunol.1303029⟩ Journal of Immunology, 193(2), 961-969 Journal of Immunology, 2014, 193 (2), pp.961-969. ⟨10.4049/jimmunol.1303029⟩ |
| بيانات النشر: | HAL CCSD, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, MESH: Minor Histocompatibility Antigens, MESH: T-Lymphocytes/metabolism, MESH: Neoplasms, Experimental/therapy, T-Lymphocytes, medicine.medical_treatment, Cell, CD8-Positive T-Lymphocytes, Lymphocyte Activation, MESH: Mice, Knockout, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Antibodies/immunology, Mice, Drug Delivery Systems, 0302 clinical medicine, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, MESH: CD8-Positive T-Lymphocytes/metabolism, MESH: Dendritic Cells/metabolism, Mice, Knockout, MESH: Nanoparticles/administration & dosage, Antigen Presentation, 0303 health sciences, Receptors, Antigen, T-Cell, gamma-delta, MESH: Antigens, CD/immunology, Tumor Burden, 3. Good health, medicine.anatomical_structure, MESH: CD8-Positive T-Lymphocytes/immunology, MESH: T-Lymphocytes, Cytotoxic/immunology, MESH: Antibodies/chemistry, MESH: Neoplasms, Experimental/immunology, MESH: Natural Killer T-Cells/metabolism, Cell activation, MESH: Tumor Burden/immunology, MESH: CD8 Antigens/metabolism, MESH: Cell Line, Tumor, MESH: Lectins, C-Type/immunology, MESH: Antigen Presentation/immunology, MESH: Mice, Transgenic, CD8 Antigens, T cell, MESH: Galactosylceramides/chemistry, Immunology, Galactosylceramides, Mice, Transgenic, Receptors, Cell Surface, chemical and pharmacologic phenomena, MESH: Receptors, Cell Surface/immunology, Biology, Antibodies, Minor Histocompatibility Antigens, 03 medical and health sciences, MESH: Natural Killer T-Cells/immunology, Immune system, Antigens, CD, MESH: Mice, Inbred C57BL, Cell Line, Tumor, MESH: T-Lymphocytes/immunology, medicine, Animals, MESH: Galactosylceramides/administration & dosage, Lectins, C-Type, MESH: T-Lymphocytes, Cytotoxic/metabolism, MESH: Receptors, Antigen, T-Cell, gamma-delta/immunology, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Mice, 030304 developmental biology, MESH: Galactosylceramides/immunology, MESH: Receptors, Antigen, T-Cell, gamma-delta/metabolism, Dendritic Cells, Neoplasms, Experimental, Dendritic cell, Immunotherapy, MESH: Drug Delivery Systems/methods, MESH: Male, MESH: Lymphocyte Activation/immunology, Mice, Inbred C57BL, MESH: Neoplasms, Experimental/pathology, MESH: Nanoparticles/chemistry, Cancer research, Nanoparticles, Natural Killer T-Cells, MESH: CD8 Antigens/immunology, CD8, T-Lymphocytes, Cytotoxic, 030215 immunology, MESH: Dendritic Cells/immunology |
| الوصف: | Immunotherapy aiming at enhancing innate and acquired host immunity is a promising approach for cancer treatment. The invariant NKT (iNKT) cell ligand α-galactosylceramide (α-GalCer) holds great promise in cancer therapy, although several concerns limit its use in clinics, including the uncontrolled response it promotes when delivered in a nonvectorized form. Therefore, development of delivery systems to in vivo target immune cells might be a valuable option to optimize iNKT cell–based antitumor responses. Using dendritic cell (DC)–depleted mice, DC transfer experiments, and in vivo active cell targeting, we show that presentation of α-GalCer by DCs not only triggers optimal primary iNKT cell stimulation, but also maintains secondary iNKT cell activation after challenge. Furthermore, targeted delivery of α-GalCer to CD8α+ DCs, by means of anti-DEC205 decorated nanoparticles, enhances iNKT cell–based transactivation of NK cells, DCs, and γδ T cells. We report that codelivery of α-GalCer and protein Ag to CD8α+ DCs triggers optimal Ag-specific Ab and cytotoxic CD8+ T cell responses. Finally, we show that targeting nanoparticles containing α-GalCer and Ag to CD8α+ DCs promotes potent antitumor responses, both in prophylactic and in therapeutic settings. Our data may have important implications in tumor immunotherapy and vaccine development. |
| اللغة: | English |
| تدمد: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.1303029⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89d564a81d30efc92538f3b7fbb6a0b5 https://www.hal.inserm.fr/inserm-02436034 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....89d564a81d30efc92538f3b7fbb6a0b5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00221767 15506606 |
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| DOI: | 10.4049/jimmunol.1303029⟩ |