Um tipo de célula imune dá uma possível explicação para as diferenças sexuais no câncer de pâncreas
A imunoterapia é uma forma eficaz de terapia para diferentes tipos de câncer. No entanto, para o câncer de pâncreas, seu efeito é limitado e difere entre homens e mulheres. Pesquisadores do Karolinska Institutet encontraram agora uma possível...
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)
Células de câncer pancreático (azul) crescendo como uma esfera envolta em membranas (vermelho). Crédito: Instituto Nacional do Câncer
A imunoterapia é uma forma eficaz de terapia para diferentes tipos de câncer. No entanto, para o câncer de pâncreas, seu efeito é limitado e difere entre homens e mulheres. Pesquisadores do Karolinska Institutet encontraram agora uma possível explicação para essa diferença entre os sexos.
O estudo, publicado na Cancer Research , revela a presença de uma célula imune em mulheres com câncer pancreático que obstrui a resposta imune do corpo. Os resultados podem abrir caminho para um tratamento mais específico para cada sexo.
“Mais e mais evidências estão chegando de que os hormônios masculinos e femininos afetam nosso sistema imunológico , mas ainda há muito a ser feito antes que o sexo possa ser incluído como um fator biológico auto-evidente na pesquisa e terapia médica”, diz o primeiro autor do artigo, Fei He. , ex-pesquisador visitante do Departamento de Medicina Laboratorial, Karolinska Institutet. "Nossos resultados fornecem novas perspectivas que podem ter alto impacto no tratamento do câncer."
Nos últimos anos, a imunoterapia, que estimula o sistema imunológico a atacar as células cancerígenas , tem contribuído significativamente para o tratamento de diferentes tipos de câncer, como melanoma e câncer de pulmão, rim e fígado . No entanto, é muito menos eficaz contra o câncer de pâncreas, que continua sendo um dos tipos de câncer mais letais que deixa os pacientes, em média, com quatro a seis meses de vida após o diagnóstico.
Diferenças com viés de sexo na resposta imune
Estudos anteriores mostraram que existem diferenças biológicas ligadas ao sexo no sistema imunológico masculino e feminino que, entre outros efeitos, determinam como os tumores crescem e a capacidade do corpo de se defender contra eles. Um estudo colaborativo envolvendo pesquisadores do Karolinska Institutet, na Suécia, abordou agora o que pode causar tais disparidades relacionadas ao sexo na resposta imune ao câncer pancreático.
O estudo demonstrou uma diferença crucial nas propriedades do tumor em homens e mulheres com câncer pancreático. Existe um tipo de célula imune presente nas mulheres que protege o tumor e impede que as células T do sistema imunológico se infiltrem no tumor e ataquem as células cancerígenas.
"Este subgrupo de células imunológicas se correlaciona com baixa sobrevivência exclusivamente em pacientes com câncer do sexo feminino", diz o autor correspondente do estudo e investigador principal Dhifaf Sarhan, professor assistente do Departamento de Medicina Laboratorial do Karolinska Institutet. "Nossos resultados mostram que as células imunes expressam uma proteína específica chamada FPR2 e podem servir tanto como um fator prognóstico específico do sexo quanto como um alvo terapêutico".
Novo alvo para imunoterapia em mulheres
Os resultados podem ser úteis para o desenvolvimento de ferramentas de diagnóstico e imunoterapia para câncer de pâncreas que levem em consideração as diferenças biológicas entre homens e mulheres. O estudo foi baseado em uma combinação de métodos, incluindo sequenciamento de RNA de célula única, proteômica, tubo de ensaio e validação de pacientes e tratamentos de modelos 3D de câncer pancreático e camundongos.
"O próximo passo é dar seguimento ao nosso novo alvo de imunoterapia para mulheres", diz o Dr. Sarhan. "Também estamos realizando análises extensas para entender como as diferenças imunológicas entre os sexos impulsionam o desenvolvimento do tumor de maneiras diferentes em pacientes com câncer masculino e feminino, com o objetivo de encontrar e desenvolver alvos de imunoterapia para cada grupo".
O estudo é o resultado de uma estreita colaboração entre o grupo de pesquisa do Dr. Sarhan e pesquisadores do Karolinska Institutet, Karolinska University Hospital, Pronoxis AB e Uppsala University na Suécia e universidades no Canadá, Cingapura e China.
Mais informações: FPR2 molda um microambiente de tumor pancreático imune excluído e conduz à exaustão de células T de maneira dependente do sexo, Cancer Research (2023). DOI: 10.1158/0008-5472.CAN-22-2932
Informações do periódico: Pesquisa sobre o câncer