Prophylactic dendritic cell vaccination controls pancreatic cancer growth in a mouse model |
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| Institution: | 1. Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA;2. Medical Student Training Program, Northwestern University, Chicago, Illinois, USA;3. Department of Radiology, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China;4. Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China;5. Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China;6. Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China;7. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA;1. Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida, USA;2. Department of Laboratory Medicine & Pathology, Mayo Clinic, Jacksonville, Florida, USA;3. Division of Internal Medicine-Clinical Hematology, Al-Azhar University, Cairo, Egypt;1. Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany;2. German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany;3. University Cancer Centrum (UCC), Early Clinical Trial Unit (ECTU), University Hospital Carl Gustav Carus, Dresden, Germany;4. Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany;5. Biotechnology Center, Center for Molecular and Cellular Bioengineering TU Dresden Tatzberg 47-49, Dresden, Germany;6. Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany;7. National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany;8. Center for Regenerative Therapies (CRTD), Dresden, Germany;1. Lanzhou University Second Hospital, Lanzhou, Gansu, China;2. Gansu Agricultural University, Lanzhou, Gansu, China;3. The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China |
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| Abstract: | PurposePancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths with high recurrence after surgery due to a paucity of effective post-surgical adjuvant treatments. DC vaccines can activate multiple anti-tumor immune responses but have not been explored for post-surgery PDAC recurrence. Intraperitoneal (IP) delivery may allow increased DC vaccine dosage and migration to lymph nodes. Here, we investigated the role of prophylactic DC vaccination controlling PDAC tumor growth with IP delivery as an administration route for DC vaccination.MethodsDC vaccines were generated using ex vivo differentiation and maturation of bone marrow–derived precursors. Twenty mice were divided into four groups (n = 5) and treated with DC vaccines, unpulsed mature DCs, Panc02 lysates or no treatment. After tumor induction, mice underwent three magnetic resonance imaging scans to track tumor growth. Apparent diffusion coefficient (ADC), a quantitative magnetic resonance imaging measurement of tumor microstructure, was calculated. Survival was tracked. Tumor tissue was collected after death and stained with hematoxylin and eosin, Masson's trichrome, terminal deoxynucleotidyl transferase dUTP nick end labeling and anti-CD8 stains for histology.ResultsDC-vaccinated mice demonstrated stronger anti-tumor cytotoxicity compared with control groups on lactate dehydrogenase assay. DC vaccine mice also demonstrated decreased tumor volume, prolonged survival and increased ΔADC compared with control groups. On histology, the DC vaccine group had increased apoptosis, increased CD8+ T cells and decreased collagen. ΔADC negatively correlated with % collagen in tumor tissues.DiscussionProphylactic DC vaccination may inhibit PDAC tumor growth during recurrence and prolong survival. ΔADC may be a potential imaging biomarker that correlates with tumor histological features. |
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