Local administration of granulocyte macrophage colony-stimulating factor induces local accumulation of dendritic cells and antigen-specific CD8+ T cells and enhances dendritic cell cross-presentation |
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| Affiliation: | 1. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States;2. Departments of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, United States;3. Departments of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, United States;4. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, United States;5. Department of Obstetrics and Gynecology, St. Vincent''s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea;6. Pharmacy School of Fudan University, Shanghai, China;7. Department of Obstetrics and Gynecology, Shanghai Tenth People''s Hospital of Tongji University, Shanghai, China;8. Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai, China;9. Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;q. Azienda Ospedaliera-Universitaria Policlinico di Modena, Italy;r. Diparimento di Diagnostica per immagini e radiologia interventistica, Ospedale S. Maria delle Grazie, Pozzuoli, Napoli, Italy;s. Università Cattolica Campobasso, Italy;t. UOC Radiologia, Polo Chirurgico Confortini, Azienda Ospedaliera Universitaria IntegrataVerona, Italy;u. Radiologia OC S. Chiara Trento, Italy;v. UOC di Radiologia OspCattinara Trieste, Italy;w. Ospedale Verilia Ca Maiore Lucca, Italy;x. Radiologia università Torino, Italy;y. Cardiologia-Radiologia Guastalla AUSL Reggio Emilia, Italy;z. UOC di Radiodiagnostica Universitaria Bari, Italy;11. Ospedale Lamezia Terme. ASP Catanzaro, Italy;12. Area di Diagnostica per Immagini, Università Campus Biomedico Roma, Italy;13. Ospedale Infermi Rimini, Italy;14. Ospedaledi Circolo Fondazione Macchi-Università degli Studi dell’InsubriaVarese, Italy;15. Università “Sapienza” Radiologia A.O. Sant’ Andrea Roma, Italy;16. Policlinico Universitario Tor Vergata Roma, Italy;17. Bassano Del Grappa Vicenza, Italy;18. Ospedale Mauriziano Umberto I Torino, Italy;19. Azienda ospedaliera G Moscati Avellino, Italy;110. Radiologia Ospedale Valduce, Como, Italy;111. Policlinico, Monza, Italy;112. Alto Vicentino Thiene Schio, Italy;113. Ospedale S. Maria della Misericordia Rovigo, Italy;114. Istituto Tecnologie Avanzate Biomediche Università Chieti -Pescara, Italy;115. Ospedale Mazzoni Ascoli Piceno, Italy;1p. IRCCS Istituto Clinico Humanitas, Rozzano Milano, Italy;1. Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Italy;2. Dipartimento di Scienze Cliniche Applicate e Biotecnologie, Università di L’Aquila, Italy;3. Cardio-Vascular Imaging Unit, Giovanni XXIII Hospital, Monastier di Treviso, TV, Italy;4. Erasmus Medical Center University, Rotterdam, The Netherlands;5. IRCCS Centro Cardiologico Monzino, Italy;6. Policlinico S. Orsola Bologna, Italy;7. Azienda ospedaliera G Brotzu Cagliari, Italy;8. IRCCS Policlinico San Donato, Radiology Unit, Milan, Italy;9. Azienda Ospedaliera Universitaria Careggi, Italy;10. Policlinico Gemelli, Università Cattolica Roma, Italy;11. Ospedale Galliera, Genova, Italy;12. Ospedale S. Anna Ferrara, Italy;13. Azienda Ospedaliera Universitaria G. Martino, Me, Italy;14. Ospedale Madre Giuseppina Vannini, Roma, Italy;15. IRCCS S. Raffaele, Università Vita Salute, Milano, Italy;p. Fate Bene Fratelli Isola tiberina, Roma, Italy;1. Center for Immunobiology and Vaccine Development, Children''s Hospital Oakland Research Institute, Oakland, CA 94609, USA;2. Department of Molecular Genetics, University of Toronto, Toronto, ON, M55 1A8 Canada;1. CEA, Division of Immuno-Virology, IDMIT Center, iMETI/DSV, Fontenay-aux-Roses, France;2. UMR-1184, Université Paris Sud 11, Orsay, France;3. Vaccine Research Institute (VRI), Créteil, France;4. INSERM, Paris, France;5. Bertin Pharma, Montigny-Le-Bretonneux, France;6. INSERM, Unite U955, Créteil F-94010, France;7. Université Paris-Est, Faculté de Médecine, Hôpital Albert-Chenevier, Créteil F-94010, France;8. Hôpital Henri-Mondor, Service d’Immunologie clinique, UMR-S 955, Créteil F-94010, France;1. Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Südufer 10, 17493 Greifswald-Insel Riems, Germany;2. Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Suedufer 10, 17493 Greifswald-Insel Riems, Germany;1. Michigan Department of Community Health, Division of Immunization, 201 Townsend, PO Box 30195, Lansing, MI 48909, United States;2. Surveillance and Data Management Branch, Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, NE MS E-02, Atlanta, GA 30333, United States;3. Epidemiology and Applied Research Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 4770 Buford Hwy, NE MS K-40, Atlanta, GA 30341, United States;4. Michigan Department of Community Health, Division for Vital Records and Health Statistics, 201 Townsend, PO Box 30195, Lansing, MI 48909, United States |
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| Abstract: | Immunotherapy has emerged as a promising treatment strategy for the control of HPV-associated malignancies. Various therapeutic HPV vaccines have elicited potent antigen-specific CD8+ T cell mediated antitumor immune responses in preclinical models and are currently being tested in several clinical trials. Recent evidence indicates the importance of local immune activation, and higher number of immune cells in the site of lesion correlates with positive prognosis. Granulocyte macrophage colony-stimulating factor (GMCSF) has been reported to posses the ability to induce migration of antigen presentation cells and CD8+ T cells. Therefore, in the current study, we employ a combination of systemic therapeutic HPV DNA vaccination with local GMCSF application in the TC-1 tumor model. We show that intramuscular vaccination with CRT/E7 DNA followed by GMCSF intravaginal administration effectively controls cervicovaginal TC-1 tumors in mice. Furthermore, we observe an increase in the accumulation of E7-specific CD8+ T cells and dendritic cells in vaginal tumors following the combination treatment. In addition, we show that GMCSF induces activation and maturation in dendritic cells and promotes antigen cross-presentation. Our results support the clinical translation of the combination treatment of systemic therapeutic vaccination followed by local GMCSF administration as an effective strategy for tumor treatment. |
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| Keywords: | Immunotherapy GM-CSF CRT/E7 Dendritic cell |
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