Avaliação da expressão da via pd-1/pdl-1 e das proteínas ctla-4, rank-rank-l e ifn-γ em mastocitomas cutâneos de alto grau em cães: novas perspectivas de uso da imunoterapia
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Data
2021-01-02
Autores
Guillén, Noelia Carolina Talavera
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O mastocitoma cutâneo (MCT) é o tumor cutâneo mais comum nos cães, sendo que os MCTs de alto grau possuem comportamento mais agressivo. A escolha do tratamento depende dos fatores prognósticos e do grau histopatológico relacionado ao tumor, porém até o momento não existem marcadores que relacionem a expressão dos tumores e possam prever a presença de metástase linfática. Desta forma, o presente estudo teve como objetivo avaliar a expressão da via PD-1/PD-L1 no linfonodo metastásico e no MCT de alto grau, assim como também avaliar a expressão da via RANK/RANK-L e das proteínas CTLA-4 e INF-γ nesse tipo do tumor, com o objetivo de determinar se trata-se de um tumor que pode ser responsivo a imunoterapia. Foram selecionados 10 pacientes com MCT de alto grau, e avaliados quanto aos dados de resenha, como idade, sexo e raça, localização do tumor, número de nódulos, presença de metástase regional e a distância, estágio clínico, tempo de so- brevida e avaliação da expressão dos checkpoints, via RANK/RANKL e do IFNy com imunomarcação variando de moderada a intensa.Os MCT de alto grau com tamanho superior a 3 cm tiveram diferença estatística, concluindo que os tumores de 3 cm ou mais independentemente das características próprias do tumor podem ja estar associados com a presença de metástase linfática. Adicionalmente, o grupo de cães inclusos apresentavam características epidemiológicas variáveis, porém podemos concluir que no caso dos MCT de alto grau independente de raça, sexo, idade e estágio clínico, a presença das vias PD1-PD-L1, RANK/RANK-L e proteínas CTLA-4 e IFN-y estão ativas. Concluiu-se que o MCT parece ser um tumor passível de manipulação imunológica através do uso da imunoterapia, sendo uma nova ferramenta para auxiliar no tratamento desses tumores.
- Cutaneous mast cell tumor (MCT) is the most common skin tumor in dogs, and high-grade MCTs have a more aggressive behavior. The choice of treatment depends on prognostic factors and the histopathological grade related to the tumor, however, to date, there are no markers that relate the expression of the tumors and can predict the presence of lymphatic metastasis. Thus, the present study aimed to evaluate the expression of the PD-1 / PD-L1 pathway in the metastatic lymph node and high-grade MCT, as well as also to evaluate the expression of the RANK / RANKL pathway and CTLA-4 proteins and INFγ in this neoplastic type, in order to determineif it is a tumor that can be responsive to immunotherapy. Nine patients with high-grade MCT were selected and evaluated for review data, such as age, sex and race, tumor location, number of nodules, presence of regional metastasis and distance, clinical stage and survival time and evaluation expression of checkpoints, via RANK / RANKL and IFNy with immunostaining ranging from moderate to intense. High-grade MCTs larger than 3 cm had a statistical difference, concluding that tumors of 3 cm or more regardless of the tumor's own characteristics may already be associated with the presence of lymphatic metastasis. Additionally, the group of dogs included had variable epidemiological characteristics, but we can conclude that in the case of high-grade MCTs regardless of race, sex, age, and clinical stage, the presence of the PD1-PDL1, RANK / RANK-L and CTLA-4 and IFN-y proteins are active. We conclude that MCT appears to be a tumor amenable to immunological manipulation through the use of immunotherapy, which is a new tool to assist in the treatment of these tumors.
- Cutaneous mast cell tumor (MCT) is the most common skin tumor in dogs, and high-grade MCTs have a more aggressive behavior. The choice of treatment depends on prognostic factors and the histopathological grade related to the tumor, however, to date, there are no markers that relate the expression of the tumors and can predict the presence of lymphatic metastasis. Thus, the present study aimed to evaluate the expression of the PD-1 / PD-L1 pathway in the metastatic lymph node and high-grade MCT, as well as also to evaluate the expression of the RANK / RANKL pathway and CTLA-4 proteins and INFγ in this neoplastic type, in order to determineif it is a tumor that can be responsive to immunotherapy. Nine patients with high-grade MCT were selected and evaluated for review data, such as age, sex and race, tumor location, number of nodules, presence of regional metastasis and distance, clinical stage and survival time and evaluation expression of checkpoints, via RANK / RANKL and IFNy with immunostaining ranging from moderate to intense. High-grade MCTs larger than 3 cm had a statistical difference, concluding that tumors of 3 cm or more regardless of the tumor's own characteristics may already be associated with the presence of lymphatic metastasis. Additionally, the group of dogs included had variable epidemiological characteristics, but we can conclude that in the case of high-grade MCTs regardless of race, sex, age, and clinical stage, the presence of the PD1-PDL1, RANK / RANK-L and CTLA-4 and IFN-y proteins are active. We conclude that MCT appears to be a tumor amenable to immunological manipulation through the use of immunotherapy, which is a new tool to assist in the treatment of these tumors.
Descrição
Palavras-chave
Cães, Checkpoints, Imunoterapia, Mastocitoma