P-MAPA activates TLR2 and TLR4 signaling while its combination with IL-12 stimulates CD4+ and CD8+ effector T cells in ovarian cancer

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorFarmabrasilis R&D Division-
Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.creatorSilveira, Henrique Spaulonci [UNESP]-
Autor(es): dc.creatorLupi, Luiz Antonio [UNESP]-
Autor(es): dc.creatorRomagnoli, Graziela Gorete [UNESP]-
Autor(es): dc.creatorKaneno, Ramon [UNESP]-
Autor(es): dc.creatorda Silva Nunes, Iseu-
Autor(es): dc.creatorFávaro, Wagner José-
Autor(es): dc.creatorde Almeida Chuffa, Luiz Gustavo [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:30:40Z-
Data de disponibilização: dc.date.available2022-02-22T00:30:40Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-08-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.lfs.2020.117786-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/200442-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/200442-
Descrição: dc.descriptionAims: Ovarian cancer (OC) is the most lethal gynecological malignancies and many women develop chemoresistance associated with the inflammatory process. We investigated the effects of P-MAPA and IL-12 on the inflammatory and immune responses in a chemically-induced OC model. Main methods: OCs were induced with 7,12-dimethylbenz(a)anthracene into the ovarian bursa, and the animals were given P-MAPA (5 mg/kg bw., i.p., twice a week), or IL-12 (300 ng/kg bw., i.p., one a week) for 60 days, or both P-MAPA and IL-12. Immunohistochemistry, western blot, flow cytometry, and multiplex assay were used to examine the effectiveness of immunotherapies in OC. Key findings: The combinatory therapy improved the general OC features, reducing inflammatory cells and adipocyte accumulation, in addition to revealing a soft and mobile tissue with no adherences and peritoneal implants. P-MAPA treatment increased the levels of TLR2, TLR4 and TRIF in OCs while decreasing the number of regulatory T (Treg) cells. Additionally, the association of P-MAPA with IL-12 significantly increased the number of CD4+ and CD8+ T effector cells in draining lymph nodes. Regarding the inflammatory mediators, P-MAPA enhanced the levels of the pro-inflammatory cytokine IL-17 while P-MAPA+IL-12 increased the levels of IL-1β. Treatment with IL-12 enhanced the cytokine levels of IL-17, TNF-α, IL-1β, and IL-2 in addition to the chemokine MIP-1α. Significance: We conclude that P-MAPA upregulated TLR2 and TLR4 signaling, possibly activating the non-canonical pathway, while attenuating the tumor immunosuppression. Also, the combination of P-MAPA with IL-12 improves the antitumor immunoresponse, opening a new therapeutic approach for fighting OC.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionDepartment of Structural and Functional Biology UNESP - São Paulo State University Institute of Biosciences-
Descrição: dc.descriptionDepartment of Microbiology and Immunology UNESP - São Paulo State University Institute of Biosciences-
Descrição: dc.descriptionFarmabrasilis R&D Division-
Descrição: dc.descriptionDepartment of Structural and Functional Biology UNICAMP - University of Campinas-
Descrição: dc.descriptionDepartment of Structural and Functional Biology UNESP - São Paulo State University Institute of Biosciences-
Descrição: dc.descriptionDepartment of Microbiology and Immunology UNESP - São Paulo State University Institute of Biosciences-
Descrição: dc.descriptionCAPES: 0708/2018-
Descrição: dc.descriptionFAPESP: 2016/03993-9-
Descrição: dc.descriptionFAPESP: 2017/03441-9-
Descrição: dc.descriptionFAPESP: 2019/00906-6-
Idioma: dc.languageen-
Relação: dc.relationLife Sciences-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectIL-12-
Palavras-chave: dc.subjectImmune cells-
Palavras-chave: dc.subjectInflammation-
Palavras-chave: dc.subjectOvarian cancer-
Palavras-chave: dc.subjectP-MAPA-
Palavras-chave: dc.subjectTLR-
Título: dc.titleP-MAPA activates TLR2 and TLR4 signaling while its combination with IL-12 stimulates CD4+ and CD8+ effector T cells in ovarian cancer-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

Não existem arquivos associados a este item.