Ptaquiloside from bracken (Pteridium spp.) inhibits tumour-infiltrating CD8+ T cells in HPV-16 transgenic mice |
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| Affiliation: | 1. ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal;2. Grupo de Oncologia Molecular e Patologia Viral, CI-IPOP, Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal;3. Serviço de Virologia, Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal;4. Liga Portuguesa Contra o Cancro — Núcleo Regional do Norte, Estrada Interior da Circunvalação, no. 6657, 4200-177 Porto, Portugal;5. LEPABE, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal;6. Centro de Investigação e Tecnologia de Ciências Agroambientais e Biológicas (CITAB), Universidade de Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5001-911 Vila Real, Portugal;7. Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal;8. CEBIMED, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal;1. CICS – Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal;2. CNC – Center of Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal;1. Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal;2. Department of Therapeutic and Diagnostic Technologies, Polytechnic Institute of Bragança (IPB), Bragança, Portugal;3. Agrarian School of Viseu, Polytechnic Institute of Viseu, Viseu, Portugal;4. Center for the Study of Education, Technologies and Health, Polytechnic Institute of Viseu, Viseu, Portugal;5. Center for the Research and Technology of Agro-Environmental and Biological Science (CITAB), UTAD, Vila Real, Portugal;6. Center for Mathematics, UTAD, Vila Real, Portugal;7. Animal and Veterinary Research Center (CECAV), UTAD, Vila Real, Portugal;1. Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal;2. Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport Sciences, University of Porto, Porto, Portugal;3. Organic Chemistry of Natural Products and Agrifood, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal;4. Animal and Veterinary Research Center (CECAV), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal;5. Center for the Study of Animal Sciences (CECA), University of Porto, Porto, Portugal;1. Department of Urology, UC San Diego Health System, San Diego, CA;2. UCSD Moores Cancer Center, La Jolla, CA;3. Naval Medical Center San Diego, San Diego, CA;4. Department of Radiology, University of California, San Diego, La Jolla, CA;5. UCSD In Vivo Cancer and Molecular Imaging Center, University of California, San Diego, La Jolla, CA;6. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA;7. Department of Surgery, University of California, San Diego, La Jolla, CA;1. Molecular Imaging Program, NCI, NIH, 10 Center Dr, MSC 1182 Bldg 10, Room B3B85, Bethesda, MD 20892-1088;2. Laboratory of Animal Medicine and Surgery NHLBI, NIH, Bethesda, Maryland;3. Laboratory Animal Science Program, Leidos Biomedical Research Inc. (formerly SAIC-Frederick, Inc.), Frederick National Laboratory for Cancer Research, Frederick, Maryland;4. Philips Research North America, Briarcliff Manor, New York;5. Urologic Oncology Branch, NCI, NIH, Bethesda, Maryland;6. Center for Interventional Oncology, NCI and Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, Maryland;7. Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc. (formerly SAIC-Frederick, Inc.), Frederick National Laboratory for Cancer Research, Frederick, Maryland |
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| Abstract: | Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of ptaquiloside on tumour-infiltrating CD8+ T lymphocytes, which are critical players in anti-tumour immunity. HPV16+/− mice received ptaquiloside (0.5 mg/mouse/week) for 10 weeks. These were then euthanized at 30 weeks of age, along with age-matched untreated controls. Skin samples were enzymatically digested and CD8+ T cells analysed for CD107a and CD44 surface expression. Ptaquiloside-exposed HPV16+/− mice showed a significantly decreased percentage (P < 0.05) of CD8+CD107a+ and CD8+CD44 + T cells when compared with untreated HPV16+/− animals. Histologically, 100% of ptaquilosidetreated mice showed diffuse epidermal dysplasia, compared with 50% of the untreated mice. These findings suggest that ptaquiloside exerts an immunosuppressive role by decreasing CD8+ T cell activation and degranulation in HPV-induced lesions. Given the key role of CD8+ T lymphocytes against HPV-induced lesions, this effect is likely to contribute for viral persistence, tumour progression and increased aggressiveness in patients with HPV-related malignancies. |
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| Keywords: | Ptaquiloside Human papillomavirus Cancer Bracken BPV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0040" }," $$" :[{" #name" :" text" ," _" :" Bovine Papillomavirus CTL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" Cytotoxic T Lymphocytes FASL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" FAS Ligand FcγR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" Fragment crystallisable gamma Receptor H&E" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" Haematoxylin & Eosin HPV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" Human Papillomavirus HSQC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" Heteronuclear Single Quantum Coherence spectroscopy IFN-γ" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" Gamma-interferon K14" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" Keratin-14 LAMP1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" Lysosome-associated Membrane Protein 1 mAb" },{" #name" :" keyword" ," $" :{" id" :" kwrd0140" }," $$" :[{" #name" :" text" ," _" :" Monoclonal Antibody MHC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" Major Histocompatibility Complex NMR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0160" }," $$" :[{" #name" :" text" ," _" :" Nuclear Magnetic Resonance NK" },{" #name" :" keyword" ," $" :{" id" :" kwrd0170" }," $$" :[{" #name" :" text" ," _" :" Natural Killer PTQ" },{" #name" :" keyword" ," $" :{" id" :" kwrd0180" }," $$" :[{" #name" :" text" ," _" :" Ptaquiloside WT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0190" }," $$" :[{" #name" :" text" ," _" :" Wild-type |
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