Monoterapia ou terapia combinada com inibidores de checkpoint imunológico: comparando efeitos aditivos e mecanismos diferenciais na resposta antitumoral
DOI:
https://doi.org/10.5281/zenodo.13729930Palavras-chave:
Inibidores de checkpoint, Anti-PD-1, Anti-CTLA-4, Terapia combinada, SinergismoResumo
O câncer é um problema de saúde pública no Brasil e no mundo, com estimativas de 18 milhões de novos casos surgindo globalmente em 2018 e mais de 600 mil novos casos no Brasil em 2020. A mortalidade relacionada à doença é alarmante, com 9,6 milhões de óbitos por câncer em 2018. As células do sistema imune, principalmente os linfócitos T CD8, desempenham um papel fundamental na defesa contra tumores. No entanto, os mecanismos de evasão imunológica, como a diminuição da expressão de MHC de classe I nas células tumorais e a ação de checkpoints imunológicos como CTLA-4 e PD-1, dificultam a eficácia da resposta imune. O CTLA-4 inibe a ativação de linfócitos, enquanto o PD-1, ao interagir com seus ligantes, limita a função dos linfócitos, favorecendo a sobrevivência tumoral. A imunoterapia de bloqueio de checkpoint, com fármacos como Ipilimumabe (anti-CTLA-4) e Nivolumabe (anti-PD-1), tem mostrado resultados promissores, aumentando a sobrevida e a resposta em pacientes com câncer. A combinação dessas terapias apresenta melhores resultados do que as monoterapias, mostrando maior eficácia e capacidade de ativação de células T efetoras. No entanto, existem preocupações quanto aos efeitos adversos e à compreensão dos mecanismos moleculares envolvidos. A terapia combinada induz um perfil de expressão de genes e uma resposta imunológica distinta, sugerindo ações sinérgicas. Apesar dos resultados encorajadores, a necessidade de mais pesquisas para compreender plenamente essa sinergia e otimizar a terapia continua evidente, a fim de melhorar a aplicação clínica e os padrões de tratamento para o câncer.
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