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Métodos Terapêuticos e Terapias MTCI
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1.
Front Immunol ; 11: 584959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33312174

RESUMO

PD-1/PD-L1 pathway plays a role in inhibiting immune response. Therapeutic antibodies aimed at blocking the PD-1/PD-L1 interaction have entered clinical development and have been approved for a variety of cancers. However, the clinical benefits are reduced to a group of patients. The research in combined therapies, which allow for a greater response, is strongly encouraging. We previously characterized a polyphenol-rich extract from Caesalpinia spinosa (P2Et) with antitumor activity in both melanoma and breast carcinoma, as well as immunomodulatory activity. We hypothesize that the combined treatment with P2Et and anti-PD-L1 can improve the antitumor response through an additive antitumor effect. We investigated the antitumor and immunomodulatory activity of P2Et and anti-PD-L1 combined therapy in B16-F10 melanoma and 4T1 breast carcinoma. We analyzed tumor growth, hematologic parameters, T cell counts, cytokine expression, and T cell cytotoxicity. In the melanoma model, combined P2Et and anti-PD-L1 therapy has the following effects: decrease in tumor size; increase in the number of activated CD4+ and CD8+ T cells; decrease in the number of suppressor myeloid cells; increase in PD-L1 expression; decrease in the frequency of CD8+ T cell expressing PD-1; improvement in the cytotoxic activity of T cells; and increase in the IFN γ secretion. In the breast cancer model, P2Et and PD-L1 alone or in combination show antitumor effect with no clear additive effect. This study shows that combined therapy of P2Et and anti-PD-L1 can improve antitumor response in a melanoma model by activating the immune response and neutralizing immunosuppressive mechanisms.


Assuntos
Anticorpos Monoclonais/imunologia , Antígeno B7-H1/imunologia , Caesalpinia/imunologia , Taninos Hidrolisáveis/imunologia , Fatores Imunológicos/imunologia , Melanoma Experimental/imunologia , Extratos Vegetais/imunologia , Animais , Antineoplásicos/imunologia , Neoplasias da Mama/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Humanos , Imunidade/imunologia , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Polifenóis/imunologia
2.
Int J Food Sci Nutr ; 67(8): 960-8, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27406472

RESUMO

In this work we characterize the interaction of pomegranate hydrolyzable tannins (HT) with hen egg-white lysozyme (HEL) and determine the effects of non-covalent tannin-protein complexes on macrophage endocytosis, processing and presentation of antigen. We isolated HT from pomegranate and complex to HEL, the resulting non-covalent tannin-protein complex was characterized by gel electrophoresis and MALDI-TOF MS. Finally, cell culture studies and confocal microscopy imaging were conducted on the non-covalent pomegranate HT-HEL protein complexes to evaluate its effect on macrophage antigen uptake, processing and presentation to T-cell hybridomas. Our results indicate that non-covalent pomegranate HT-HEL protein complexes modulate uptake, processing and antigen presentation by mouse peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL alone, whereas a non-covalent pomegranate HT-HEL complex had already reached maximum IL-2 expression. Pomegranate HT may increase rate of endocytose of HEL and subsequent expression of IL-2 by the T-cell hybridomas.


Assuntos
Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/imunologia , Lythraceae/química , Lythraceae/imunologia , Muramidase/química , Muramidase/imunologia , Animais , Apresentação de Antígeno , Técnicas de Cocultura , Suplementos Nutricionais/análise , Proteínas do Ovo/química , Proteínas do Ovo/imunologia , Alimento Funcional/análise , Humanos , Hibridomas/imunologia , Macrófagos Peritoneais/imunologia , Camundongos , Complexos Multiproteicos/química , Complexos Multiproteicos/imunologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Linfócitos T/imunologia
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