title: Ptaquiloside from bracken (Pteridium spp.) inhibits tumour-infiltrating CD8+T cells in HPV-16 transgenic mice.
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.
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal. Electronic address: carlos.e.santos792@gmail.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Santos
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ferreirinha
authors.affiliation: 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; Serviço de Virologia, Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sousa
authors.affiliation: 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; Serviço de Virologia, Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; Liga Portuguesa Contra o Cancro - Núcleo Regional do Norte, Estrada Interior da Circunvalação, no. 6657, 4200-177 Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Ribeiro
authors.affiliation: LEPABE, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
authors.forename: Margarida M S M
authors.initials: MM
authors.lastname: Bastos
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; 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; 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.
authors.forename: Tiago
authors.initials: T
authors.lastname: Neto
authors.affiliation: 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; Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; 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; Serviço de Virologia, Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; Liga Portuguesa Contra o Cancro - Núcleo Regional do Norte, Estrada Interior da Circunvalação, no. 6657, 4200-177 Porto, Portugal; CEBIMED, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vilanova
authors.affiliation: 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; LEPABE, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Gil da Costa
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002273:Carcinogens / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D007189:Indans / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D030361:Papillomavirus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D032498:Pteridium / Q000737:chemistry*; D012717:Sesquiterpenes / Q000633:toxicity*; D012871:Skin Diseases / Q000209:etiology* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000473:pathology
chemical_list: D002273:Carcinogens; D007189:Indans; D012717:Sesquiterpenes; C043680:ptaquiloside
keywords: Bracken; CD8(+) T cells; Cancer; Human papillomavirus; Ptaquiloside