Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo
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| Data de Publicação: | 2019 |
| Tipo de documento: | Dissertação |
| Idioma: | por |
| Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFTM |
| Texto Completo: | http://bdtd.uftm.edu.br/handle/tede/833 |
Resumo: | A ativação da imunidade adaptativa mediada por linfócitos T citotóxicos (LTC) e células natural killer (NK) é controlada pela expressão de receptores e moléculas inibitórias, que atuam prevenindo a exacerbação imunológica e apoptose por excesso de ativação. As células tumorais são capazes utilizar estes mesmos ligantes como mecanismo de escape tumoral, inibindo o reconhecimento e ativação das células efetoras, levando-as ao estado de irresponsividade. Alterações no funcionamento do sistema imune podem interferir diretamente na sobrevida do paciente. Por isso, informações a respeito do perfil imunológico são necessários para o desenvolvimento de uma terapia individualizada para o tratamento destas doenças. Neste estudo foi avaliada a expressão gênica de receptores e moléculas inibitórias e de proteínas citolíticas em pacientes com linfoma não-Hodgkin (LNH) e mieloma múltiplo (MM) em comparação a indivíduos saudáveis. O aumento na expressão gênica de granzima B associado a redução na expressão de Fas-L e PD-L1 demonstrou a ativação do sistema imunológico em pacientes com LNH. A redução dos níveis das moléculas inibitórias atuou como fator ativador da resposta imune, que poderia acarretar na inibição da autorregulação das células efetoras, levando-as a maior ativação e atividade citotóxica do sistema imunológico. Por sua vez, na ausência de expressões significativas, a redução do sistema imunológico em pacientes com MM pode ser comprovada pelas correlações inversamente proporcionais entre as proteínas citolíticas e receptores ou moléculas inibitórios. Neste cenário, o aumento na expressão das moléculas inibitórias atua simultaneamente às células tumorais, promovendo uma regulação negativa do sistema imunológico, auxiliando no processo de imunorregulação. A próxima etapa deste estudo é correlacionar a expressão destes fatores tanto no sangue periférico quanto no microambiente tumoral, em conjunto com a análise de sobrevida, para um melhor entendimento destes mecanismos na resposta imune. |
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Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiploPerforina.Granzima B.Fas.Fas-L.CD86.PD-1.PD-L1.CTLA-4.TIM-3.MARCH-1.Linfoma não-Hodgkin.Mieloma múltiplo.Receptores inibitórios de células T.qPCR.Perforin.Granzyme B.Fas.Fas-L.CD86.PD-1.PD-L1.CTLA-4.TIM-3.MARCH-1.Non-Hodgkin lymphoma.multiple myeloma.T cell inhibitory receptors.qPCR.ImunogenéticaA ativação da imunidade adaptativa mediada por linfócitos T citotóxicos (LTC) e células natural killer (NK) é controlada pela expressão de receptores e moléculas inibitórias, que atuam prevenindo a exacerbação imunológica e apoptose por excesso de ativação. As células tumorais são capazes utilizar estes mesmos ligantes como mecanismo de escape tumoral, inibindo o reconhecimento e ativação das células efetoras, levando-as ao estado de irresponsividade. Alterações no funcionamento do sistema imune podem interferir diretamente na sobrevida do paciente. Por isso, informações a respeito do perfil imunológico são necessários para o desenvolvimento de uma terapia individualizada para o tratamento destas doenças. Neste estudo foi avaliada a expressão gênica de receptores e moléculas inibitórias e de proteínas citolíticas em pacientes com linfoma não-Hodgkin (LNH) e mieloma múltiplo (MM) em comparação a indivíduos saudáveis. O aumento na expressão gênica de granzima B associado a redução na expressão de Fas-L e PD-L1 demonstrou a ativação do sistema imunológico em pacientes com LNH. A redução dos níveis das moléculas inibitórias atuou como fator ativador da resposta imune, que poderia acarretar na inibição da autorregulação das células efetoras, levando-as a maior ativação e atividade citotóxica do sistema imunológico. Por sua vez, na ausência de expressões significativas, a redução do sistema imunológico em pacientes com MM pode ser comprovada pelas correlações inversamente proporcionais entre as proteínas citolíticas e receptores ou moléculas inibitórios. Neste cenário, o aumento na expressão das moléculas inibitórias atua simultaneamente às células tumorais, promovendo uma regulação negativa do sistema imunológico, auxiliando no processo de imunorregulação. A próxima etapa deste estudo é correlacionar a expressão destes fatores tanto no sangue periférico quanto no microambiente tumoral, em conjunto com a análise de sobrevida, para um melhor entendimento destes mecanismos na resposta imune.The activation of adaptive immunity mediated by cytotoxic T lymphocytes (CTL) and natural killer (NK) is controlled by expression of inhibitory receptors and molecules, which act by preventing exacerbation and immune activation by excessive apoptosis. Tumor cells are able to use these same ligands as a mechanism of tumor escape, by inhibiting the recognition and activation of effector cells, leading to the state of irresponsiveness. Changes in the functioning of the immune system can directly interfere with therapeutic response and / or prognosis of the disease. Therefore, information regarding the immunological profile is necessary for the development of an individualized therapy for the treatment of these diseases. In this study, we evaluated the gene expression of cytolytic protein and inhibitory receptors or molecules in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) compared to healthy individuals. The increase in granzyme B gene expression associated with reduced expression of Fas-L and PD-L1 demonstrated the activation of the immune system in patients with NHL. The reduction in the levels of inhibitory molecules served as activating factor immune response, which could result in inhibition of self-regulation of effector cells, leading to greater activation and the cytotoxic activity of the immune system. In turn, in the absence of significant expressions, the reduction of the immune system in MM patients can be proved by the inversely proportional correlations between cytolytic proteins and inhibitory receptors or molecules. In this scenario, the increase in the expression of the inhibitory molecules acts simultaneously to the tumor cells, promoting a negative regulation of the immune system, aiding in the process of immunoregulation. The next step of this study is to correlate the expression of these factors in both peripheral blood and in the tumor microenvironment in conjunction with survival analysis for a better understanding of these mechanisms in the immune response.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundação de Amparo à Pesquisa do Estado de Minas GeraisUniversidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da SaúdeBrasilUFTMPrograma de Pós-Graduação em Ciências da SaúdeSOUZA, Helio Moraes de10804528691http://lattes.cnpq.br/0502276939556083VITO, Fernanda Bernadelli de05893164601http://lattes.cnpq.br/1125407492198560CALADO, Marianna Licati2019-08-26T14:35:40Z2019-03-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfCALADO, Marianna Licati. 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Blood. v. 117, n. 17, p. 4501-4510, 2011.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTM2019-09-02T17:05:52Zoai:bdtd.uftm.edu.br:tede/833Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br||bdtd@uftm.edu.bropendoar:2019-09-02T17:05:52Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false |
| dc.title.none.fl_str_mv |
Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo |
| title |
Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo |
| spellingShingle |
Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo CALADO, Marianna Licati Perforina. Granzima B. Fas. Fas-L. CD86. PD-1. PD-L1. CTLA-4. TIM-3. MARCH-1. Linfoma não-Hodgkin. Mieloma múltiplo. Receptores inibitórios de células T. qPCR. Perforin. Granzyme B. Fas. Fas-L. CD86. PD-1. PD-L1. CTLA-4. TIM-3. MARCH-1. Non-Hodgkin lymphoma. multiple myeloma. T cell inhibitory receptors. qPCR. Imunogenética |
| title_short |
Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo |
| title_full |
Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo |
| title_fullStr |
Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo |
| title_full_unstemmed |
Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo |
| title_sort |
Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo |
| author |
CALADO, Marianna Licati |
| author_facet |
CALADO, Marianna Licati |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
SOUZA, Helio Moraes de 10804528691 http://lattes.cnpq.br/0502276939556083 VITO, Fernanda Bernadelli de 05893164601 http://lattes.cnpq.br/1125407492198560 |
| dc.contributor.author.fl_str_mv |
CALADO, Marianna Licati |
| dc.subject.por.fl_str_mv |
Perforina. Granzima B. Fas. Fas-L. CD86. PD-1. PD-L1. CTLA-4. TIM-3. MARCH-1. Linfoma não-Hodgkin. Mieloma múltiplo. Receptores inibitórios de células T. qPCR. Perforin. Granzyme B. Fas. Fas-L. CD86. PD-1. PD-L1. CTLA-4. TIM-3. MARCH-1. Non-Hodgkin lymphoma. multiple myeloma. T cell inhibitory receptors. qPCR. Imunogenética |
| topic |
Perforina. Granzima B. Fas. Fas-L. CD86. PD-1. PD-L1. CTLA-4. TIM-3. MARCH-1. Linfoma não-Hodgkin. Mieloma múltiplo. Receptores inibitórios de células T. qPCR. Perforin. Granzyme B. Fas. Fas-L. CD86. PD-1. PD-L1. CTLA-4. TIM-3. MARCH-1. Non-Hodgkin lymphoma. multiple myeloma. T cell inhibitory receptors. qPCR. Imunogenética |
| description |
A ativação da imunidade adaptativa mediada por linfócitos T citotóxicos (LTC) e células natural killer (NK) é controlada pela expressão de receptores e moléculas inibitórias, que atuam prevenindo a exacerbação imunológica e apoptose por excesso de ativação. As células tumorais são capazes utilizar estes mesmos ligantes como mecanismo de escape tumoral, inibindo o reconhecimento e ativação das células efetoras, levando-as ao estado de irresponsividade. Alterações no funcionamento do sistema imune podem interferir diretamente na sobrevida do paciente. Por isso, informações a respeito do perfil imunológico são necessários para o desenvolvimento de uma terapia individualizada para o tratamento destas doenças. Neste estudo foi avaliada a expressão gênica de receptores e moléculas inibitórias e de proteínas citolíticas em pacientes com linfoma não-Hodgkin (LNH) e mieloma múltiplo (MM) em comparação a indivíduos saudáveis. O aumento na expressão gênica de granzima B associado a redução na expressão de Fas-L e PD-L1 demonstrou a ativação do sistema imunológico em pacientes com LNH. A redução dos níveis das moléculas inibitórias atuou como fator ativador da resposta imune, que poderia acarretar na inibição da autorregulação das células efetoras, levando-as a maior ativação e atividade citotóxica do sistema imunológico. Por sua vez, na ausência de expressões significativas, a redução do sistema imunológico em pacientes com MM pode ser comprovada pelas correlações inversamente proporcionais entre as proteínas citolíticas e receptores ou moléculas inibitórios. Neste cenário, o aumento na expressão das moléculas inibitórias atua simultaneamente às células tumorais, promovendo uma regulação negativa do sistema imunológico, auxiliando no processo de imunorregulação. A próxima etapa deste estudo é correlacionar a expressão destes fatores tanto no sangue periférico quanto no microambiente tumoral, em conjunto com a análise de sobrevida, para um melhor entendimento destes mecanismos na resposta imune. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019-08-26T14:35:40Z 2019-03-14 |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
| format |
masterThesis |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
CALADO, Marianna Licati. Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo. 2019. 79f . Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2019 . http://bdtd.uftm.edu.br/handle/tede/833 |
| identifier_str_mv |
CALADO, Marianna Licati. Avaliação da expressão de proteínas citolíticas e moléculas inibitórias na regulação da atividade citotóxica em pacientes com linfoma não-Hodgkin e mieloma múltiplo. 2019. 79f . Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2019 . |
| url |
http://bdtd.uftm.edu.br/handle/tede/833 |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.relation.none.fl_str_mv |
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