Relação entre as células dendríticas e os linfócitos T regulatórios em neoplasias mamárias caninas
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Data
2017-11-16
Autores
Rosolem, Mayara Caroline
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Universidade Estadual Paulista (Unesp)
Resumo
Os tumores mamários malignos possuem várias formas de evadir o sistema imune e, dentre elas está a modulação das células dendríticas (DCs), por interferência na sua maturação, resultando em apresentação de antígenos ineficiente aos linfócitos T e consequente indução da tolerância imunológica. As DCs moduladas pelo tumor recrutam muitos linfócitos T regulatórios (Tregs) para o microambiente tumoral, o que amplia os efeitos imunossupressores locais. A forte relação entre as DCs e os linfócitos Tregs no microambiente tumoral ainda foi pouco estudada, principalmente em cães. Por isso, este estudo teve o objetivo de avaliar a relação existente entre as DCs e os linfócitos Tregs em carcinomas mamários caninos do tipo simples de cadelas, por meio da técnica de imunohistoquímica. Foram utilizadas 10 amostras de glândula mamária sem tumor (G1) e 40 amostras de neoplasias mamárias (G2: adenomas; G3: carcinomas papilares; G4: carcinomas tubulares e G5: carcinomas sólidos), que foram submetidas a imunodetecção de linfócitos Treg (FOXP3+), linfócitos T CD4 e T CD8, MHC-II, DCs mieloides (imaturas e maduras), as citocinas TGF-β, IL-10, a enzima Indoleamine 2,3-dioxigenase (IDO) e dos receptores de quimiocina (CCR6 e CCR7). A maioria das células, citocinas e receptores imunológicos mostraram correlação positiva dentro da população tumoral e controles avaliados, principalmente sobre o efeito fixo “idade”, que teve alta correlação positiva com o tamanho tumoral e com CCR6. Quanto às correlações negativas, o anticorpo CD83 foi o único que não teve correlação significativa positiva com nenhuma outra variável. Observou-se que houve ocorreu relação entre as DCs mieloides imaturas/maduras e linfócitos Tregs, bem como TGF-β e IL-10, e a enzima IDO apresentaram marcante presença nas amostras malignas. A imunodetecção de CCR6 e CCR7 ocorreu principalmente nos tumores mais agressivos, onde CCR6 teve alta relação com as pacientes mais idosas e com tumores maiores, o que, no final de tudo pode refletir que o envelhecimento do sistema imunológico possa ser mais um fator pró-tumoral.
The malignant mammary tumors have several ways of evading the immune system, including the modulation of dendritic cells (DCs), by interfering with their maturation, resulting in inefficient presentation of antigens to T cells and consequent induction of immunological tolerance. Tumor-modulated DCs recruit many regulatory T cells (Tregs) into the tumor microenvironment, which amplifies local immunosuppressive effects. The strong relationship between DCs and Tregs cells into the tumor microenvironment was poorly studied, especially in dogs. Therefore, this study aimed to evaluate the relationship between DCs and Tregs cells in the simple type canine mammary carcinomas, using the immunohistochemical technique. Ten samples of mammary gland without tumor (G1) and 40 samples of mammary neoplasms (G2: adenomas, G3: papillary carcinomas, G4: tubular carcinomas and G5: solid carcinomas) were submitted to immunodetection of Treg cells (FOXP3 +), CD4 and CD8 T cells, MHC-II, myeloid DCs (immature and mature), cytokines TGF-β, IL10, Indoleamine 2,3-dioxygenase (IDO) and chemokine receptors (CCR6 and CCR7). Most of the cells, cytokines and immunological receptors showed positive correlation within the tumor population and controls evaluated, mainly on the fixed effect "age” that had high positive correlation with the tumor size and with CCR6. As for the negative correlations, the CD83 antibody was the only one that had no significant positive correlation with any other variable. It was observed that there was a relationship between immature / mature myeloid DCs and Tregs cells, as well as TGFβ and IL-10, and the IDO enzyme showed a marked presence in the malignant samples. Immunodetection of CCR6 and CCR7 occurred mainly in the most aggressive tumors, where CCR6 had a high relation with older patients and with larger tumors, which, in the end, may reflect that the aging of the immune system may be more of a pro- tumor.
The malignant mammary tumors have several ways of evading the immune system, including the modulation of dendritic cells (DCs), by interfering with their maturation, resulting in inefficient presentation of antigens to T cells and consequent induction of immunological tolerance. Tumor-modulated DCs recruit many regulatory T cells (Tregs) into the tumor microenvironment, which amplifies local immunosuppressive effects. The strong relationship between DCs and Tregs cells into the tumor microenvironment was poorly studied, especially in dogs. Therefore, this study aimed to evaluate the relationship between DCs and Tregs cells in the simple type canine mammary carcinomas, using the immunohistochemical technique. Ten samples of mammary gland without tumor (G1) and 40 samples of mammary neoplasms (G2: adenomas, G3: papillary carcinomas, G4: tubular carcinomas and G5: solid carcinomas) were submitted to immunodetection of Treg cells (FOXP3 +), CD4 and CD8 T cells, MHC-II, myeloid DCs (immature and mature), cytokines TGF-β, IL10, Indoleamine 2,3-dioxygenase (IDO) and chemokine receptors (CCR6 and CCR7). Most of the cells, cytokines and immunological receptors showed positive correlation within the tumor population and controls evaluated, mainly on the fixed effect "age” that had high positive correlation with the tumor size and with CCR6. As for the negative correlations, the CD83 antibody was the only one that had no significant positive correlation with any other variable. It was observed that there was a relationship between immature / mature myeloid DCs and Tregs cells, as well as TGFβ and IL-10, and the IDO enzyme showed a marked presence in the malignant samples. Immunodetection of CCR6 and CCR7 occurred mainly in the most aggressive tumors, where CCR6 had a high relation with older patients and with larger tumors, which, in the end, may reflect that the aging of the immune system may be more of a pro- tumor.
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células apresentadoras de antígeno, tumor de mama, cadelas, células regulatórias, imunossupressão, microambiente, Antigen presenting cells, Mammary gland tumor, Female dogs, Regulatory cells, Immunosuppression, Microenvironment