Resposta Imunológica no Melanoma: Base para a Compreensão do Papel da Imunoterapia com Inibidores de “Checkpoints” Imunológicos
Resumo
O conhecimento do processo de evolução tumoral é essencial para compreender os alvos terapêuticos no controle da doença. A forma como o sistema imune influência o desenvolvimento e a progressão do cancro é uma questão desafiante na área da imunologia. Atualmente reconhece-se o papel paradoxal do sistema imunológico neste processo: por um lado protege contra o crescimento tumoral, destruindo células exprimindo antigénios tumorais “aberrantes”, por outro pode favorecer a sua progressão, selecionando células tumorais que escapam à vigilância imunológica e são capazes de sobreviver num hospedeiro imunocompetente. Esta observação deu origem ao conceito de “cancer immunoediting”, que explica a influência do sistema imune na progressão tumoral. Tendo em conta algumas observações associadas ao melanoma, como por exemplo, o desenvolvimento de vitiligo, a possibilidade de regressão e a correlação com a imunossupressão, este tem sido considerado um exemplo de tumor imunogénico, cujo mecanismo patofisiológico reconhecido até à data se enquadra no conceito de “immunoediting”. Reconhecida a importância de CTLA-4 (antigénio linfócitário T citotóxico) e PD-1 (proteína de morte celular programada) como “checkpoints” imunológicos na regulação da atividade das células T em resposta à progressão tumoral, estas moléculas têm sido considerados alvos terapêuticos importantes no tratamento do melanoma avançado. O presente artigo pretende rever sucintamente o processo de evolução tumoral e respetiva interação com o sistema imune, bem como o mecanismo de ação dos “checkpoints” inibitórios por forma a melhor compreender os novos alvos da imunoterapia no melanoma avançado, que serão revistos em trabalho futuro.
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