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Previous issue date: 2018-03-07 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introduction: Individuals who have experienced childhood maltreatment (CM) present a higher sensitive profile to stress. This profile have been associated with dysregulation of the immune system, characterized by reactivation of herpesvirus and increased cellular senescence markers. New traumatic or stressful experiences, such as breast cancer diagnosis, in those sensitized individuals can trigger an increase in stress levels possibly leading to important immunological changes. Here we investigate the presence of immunosenescence markers in women newly diagnosed with breast cancer with and without history of CM. Methods: Twenty-nine women newly diagnosed with breast cancer, without start the treatment, were recruited. Fifteen with history of CM (CM+) and fourteen without history of CM (CM-). Twenty-seven women without breast cancer and CM were selected as the control group. Peripheral blood was assessed by lymphocyte subsets by flow cytometry (B cells, CD4+, CD8+, NK cells, activated T cell, regulatory T cell, early and intermediated T cell, senescent and exhaustion T cells. CMV serology was determinate by ELISA method. Results: The groups CM+ and CM- present similar cancer stage and family history of breast cancer. In peripheral lymphocyte subpopulations we found significantly reduced Early-differentiated T cell (p <0.0001), while intermediate-differentiated T cell (p<0.0001), senescence T cell (p<0.0001) and exhaustion t cells (p<0.0001) were increased in CM+ and CM? patients. The mean fluorescent intensity (MFI) was analyzed and the CD27 expression on CD4 T cells was found lower in controls as compared to CM+ and CM? groups (p = 0.002).There was no difference of CMV IgG levels between CM + and CM? groups (p=0.24), but between controls and CM groups, this association becomes significant (p= 0.008) . Conclusion: Our findings suggest that the presence of CM is not directly related with immunosenescence in women newly diagnosed with breast cancer. However, when evaluated women with breast cancer and healthy controls, this senescent profile is evident. Future longitudinal studies are necessary to explore the role of senescent cells in the disease progression and treatment response. / Introdu??o: Indiv?duos que foram expostos a maus tratos na inf?ncia apresentam um perfil de sensibilidade ao estresse mais acentuado, quando comparado a aqueles que cresceram em um ambiente adequado. Esse perfil est? relacionado com a desregula??o do sistema imunol?gico, sendo caracterizado pela presen?a de um aumento de marcadores de senesc?ncia celular e reativa??es de infec??es virais latentes. O acontecimento de novas experi?ncias traum?ticas, como o diagn?stico do c?ncer de mama, pode acarretar em um aumento dos n?veis relacionados ao estresse, provocando altera??es imunol?gicas importantes. Nesse estudo n?s investigamos a presen?a de marcadores de imunossenesc?ncia em mulheres rec?m diagnosticadas com c?ncer de mama com ou sem hist?rico de c?ncer de mama. M?todos: Vinte e nove pacientes rec?m diagnosticadas com c?ncer de mama foram recrutadas para esse estudo, sendo que quinze mulheres reportaram presen?a de maus tratos na inf?ncia (CM+), enquanto quatorze n?o vivenciaram situa??es envolvendo abuso ou neglig?ncia nesse mesmo per?odo (CM-). Para compor o grupo controle, foram selecionadas vinte e sete mulheres sem c?ncer de mama e que negaram a presen?a de maus tratos. Os linf?citos foram isolados das c?lulas mononucleares do sangue perif?rico (PBMCs), e imunofenotipados por citometria de fluxo para investigar a presen?a dos seguintes subgrupos: c?lulas B, CD4+, CD8+, c?lulas NK, c?lulas T ativadas, c?lulas T reguladoras, c?lulas T rec?m diferenciadas, c?lulas T intermedi?rias, c?lulas T senescentes e com perfil de exaust?o. A sorologia IgG para citomegalov?rus (CMV) foi realizada atrav?s do m?todo ELISA. Resultados: Os grupos CM+ e CM- n?o apresentaram diferen?as significativas em rela??o ao estadiamento da doen?a ou hist?rico familiar. Nas subpopula??es de linf?citos encontramos uma redu??o significativa de c?lulas T rec?m diferenciadas (p <0.0001), nos grupos CM+ e CM-, enquanto c?lulas T intermedi?rias (p <0.0001), senescentes (p <0.0001) e de exaust?o (p <0.0001) apresentaram-se aumentadas nos mesmos grupos. Ao analisar a m?dia da intensidade de fluoresc?ncia (MFI) encontramos uma express?o diminu?da de CD27 em c?lulas T CD4 nos controles quando comparado as mulheres com c?ncer de mama expostas e n?o expostas a maus tratos (p = 0.002). N?o observamos diferen?as entre os grupos CM+ e CM- em rela??o a sorologia IgG para citomegalov?rus entre os grupos CM + e CM - (p=0.24), entretanto foi presenciado entre os controles e indiv?duos com maus tratos (p= 0.008). Conclus?o: nossos achados sugerem que a presen?a de maus tratos n?o est? diretamente associada com um perfil de imunossenesc?ncia em mulheres rec?m diagnosticada com c?ncer de mama. Entretanto, quando avaliamos mulheres com c?ncer de mama e indiv?duos saud?veis esse perfil senescente torna-se evidente. Logo, torna-se necess?rio a realiza??o de novos estudos para explorar o impacto da presen?a de marcadores de senesc?ncia no tratamento e progn?stico do c?ncer de mama.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/8296 |
| Date | 07 March 2018 |
| Creators | Trintinaglia, Lauren |
| Contributors | Bauer, Mois?s Evandro |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Gerontologia Biom?dica, PUCRS, Brasil, Escola de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 4438661476953179033, 500, 600, 500, 600, -224747486637135387, -969369452308786627, 2075167498588264571 |
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