Dois novos estudos mostram como as bactérias podem ajudar os tumores a progredir e resistir ao tratamento
Dois novos estudos de pesquisadores do Fred Hutchinson Cancer Center, em Seattle, revelam como as bactérias se infiltram nos tumores e podem estar ajudando os tumores a progredir e se espalhar. A equipe de pesquisa também mostrou que os...
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)
Domínio público
Dois novos estudos de pesquisadores do Fred Hutchinson Cancer Center, em Seattle, revelam como as bactérias se infiltram nos tumores e podem estar ajudando os tumores a progredir e se espalhar. A equipe de pesquisa também mostrou que os diferentes agentes microbianos no microbioma de um tumor podem influenciar a forma como o câncer responde ao tratamento.
As descobertas também sugerem uma ligação entre a saúde bucal e o câncer , já que os micróbios na boca estão associados a cânceres em outras partes do corpo.
Os dois artigos - um publicado em 15 de novembro na Cell Reports e o outro publicado em 16 de novembro na Nature - concentram-se em uma bactéria oral chamada Fusobacterium nucleatum , que tem sido associada ao câncer colorretal .
Os tumores geralmente têm ajuda em seus esforços para sobreviver e crescer. Células não cancerígenas ao redor de um tumor podem ajudá-lo a evitar ataques do sistema imunológico , resistir a terapias direcionadas a elas e permitir que ele se espalhe para outras partes do corpo. Os pesquisadores agora estão descobrindo que alguns desses vizinhos úteis nem mesmo são células humanas — são bactérias .
“O que estamos mostrando é que existem regiões do tumor que são fortemente colonizadas por bactérias – micro-regiões de nicho – e diferem funcionalmente de regiões que não abrigam bactérias”, disse Fred Hutch, pesquisador do microbioma do câncer e co-líder do estudo. Susan Bullman, Ph.D., referindo-se ao trabalho descrito no estudo da Nature. "E essas regiões ricas em bactérias aumentaram o potencial metastático."
Bullman e seu colaborador, o microbiologista molecular Fred Hutch, Christopher D. Johnston, Ph.D., combinaram observações de tumores com experimentos de laboratório e testes de drogas de moléculas pequenas para mostrar que F. nucleatum pode moldar as condições dos tumores para mantê-los a salvo de ataque imunológico e ajudá-los a se espalhar pelo corpo. Eles descobriram que algumas terapêuticas contra o câncer podem funcionar porque visam não apenas as células tumorais, mas também as bactérias que as estão ajudando.
A equipe de pesquisa, que inclui o primeiro autor Jorge Galeano Niño, pesquisador de pós-doutorado na Fred Hutch, também descobriu que outros micróbios - incluindo o inseto intestinal Escherichia coli , ou E. coli - podem tornar um medicamento antimicrobicida e quimioterápico ineficaz, o que poderia proteger tanto o tumor quanto o F. nucleatum do tratamento. Essas descobertas podem ajudar os pesquisadores a desenvolver novas estratégias para tratar ou direcionar o câncer, abordando seu microbioma.
“Este trabalho está na interseção da pesquisa sobre câncer e microbioma”, disse Bullman. “Há dados emergentes convincentes que sugerem que quase todos os principais tipos de câncer abrigam uma microbiota intratumoral”.
Uma associação com bactérias pode parecer lógica no câncer colorretal, mas os tumores de mama, pâncreas e pulmão estão entre outros tipos de câncer que demonstraram abrigar comunidades microbianas, e estudos mostram que os microbiomas tumorais podem moldar o desenvolvimento, a progressão e a resposta ao tratamento.
Adaptando uma tecnologia de ponta que permite aos pesquisadores detectar onde os genes são ativados e desativados em fatias de tecido tumoral – transcriptômica espacial – a equipe descobriu que uma variedade de espécies bacterianas vivia dentro de cânceres orais e colorretais , mas não se espalharam uniformemente.
"Observamos hotspots bacterianos, ou micro-nichos, que abriram uma série de questões sobre como eles se formaram e podem estar afetando a biologia do câncer", disse Johnston.
As regiões colonizadas por bactérias eram altamente imunossupressoras e tinham menos células T que matam o câncer do que outras áreas. Áreas que tinham células T perto de bactérias também tiveram uma regulação positiva das proteínas do ponto de controle imunológico, que restringem os efeitos das células T que matam o câncer. Vários inibidores de checkpoint são aprovados para uso no câncer colorretal, e este estudo pode ajudar a explicar como a microbiota de um paciente pode influenciar se o câncer responde a um inibidor de checkpoint.
Descobertas específicas dos estudos:
Regiões com bactérias eram mais propensas a serem necróticas – morrendo – com menos células em divisão. Ironicamente, de acordo com outras pesquisas, isso pode estar associado à metástase porque as células se quebram e viajam para locais distantes no corpo.
No laboratório, os pesquisadores cultivaram esferoides de câncer colorretal, que são células tumorais cultivadas em aglomerados 3D, com células imunológicas chamadas neutrófilos, que reduzem a migração e invasão de células T. Os neutrófilos se espalham através de esferoides sem bactérias. Mas naqueles com bactérias, os neutrófilos migraram para o centro do esferoide e ficaram presos – uma descoberta que poderia explicar por que existem poucas células T em regiões colonizadas por bactérias.
As células tumorais nos esferoides se moveram de maneira diferente quando as bactérias estavam presentes. Em vez de se moverem em massa como um grupo, as células epiteliais do câncer migraram como células únicas, trazendo bactérias com elas. Isso é consistente com o trabalho anterior de Bullman mostrando que F. nucleatum frequentemente pega carona com metástases de câncer colorretal.
As células tumorais infectadas com bactérias aumentaram os genes associados à progressão e metástase do câncer. Em amostras de tumores orais, os pesquisadores observaram que as bactérias infectavam preferencialmente células epiteliais cancerígenas e células imunológicas específicas dentro dos tumores dos pacientes. As células tumorais infectadas aumentaram a sinalização de danos ao DNA, uma característica do câncer. Essas descobertas apoiam bactérias com um papel direto na formação dessas regiões de micro-nicho, disseram os pesquisadores.
Alguns medicamentos anticancerígenos podem ser eficazes porque também são antimicrobianos que têm como alvo as bactérias que suportam o desenvolvimento do tumor . A bactéria promotora do câncer F. nucleatum é altamente sensível a um quimioterápico comum chamado 5-fluorouracil, ou 5-FU, mas os pesquisadores descobriram que a bactéria E. coli protegia as células de câncer colorretal do 5-FU. E. coli aparentemente tem uma maneira de metabolizar a droga e minimizar sua exposição a células cancerígenas ou outras bactérias. “As descobertas mostram que os micróbios intratumorais não são espectadores inocentes durante a progressão da doença e sugerem que a microbiota deve ser levada em consideração ao pensar em tratamentos ideais para o câncer”, disse Johnston.
Relacionado a esses estudos, os pesquisadores estão estudando possíveis ligações entre a saúde bucal e o risco de câncer.
"Há uma tendência emergente de micróbios tradicionalmente associados a doenças inflamatórias orais sendo encontrados em associação com cânceres extra-orais e gastrointestinais - o que destaca a cavidade oral como um terreno fértil para onco-micróbios patogênicos", disse Johnston.
Além de permitir que os patógenos se espalhem para novas áreas do corpo, é possível que a inflamação na boca, na forma de doença periodontal ou endodôntica, possa estar selecionando e estimulando o crescimento de bactérias mais especializadas para o crescimento em condições adversas. condições e capaz de escapar do ataque imunológico, disse ele.
A equipe de pesquisa continuará explorando a possibilidade de tornar os tumores mais responsivos à imunoterapia ou quimioterapia, manipulando o microbioma, e eles estão buscando projetar terapias moduladoras do microbioma que prevenirão e tratarão o câncer e impedirão sua propagação. Mostrando que os micróbios se agrupam em áreas de tumores de difícil acesso, eles já esclareceram alguns dos obstáculos que terão que superar para desenvolver essas novas abordagens.
"Esta abordagem holística para avaliar o microambiente do tumor , que é um ecossistema multi-espécies, irá avançar nossa compreensão da biologia do câncer , e acredito que irá revelar novas vulnerabilidades terapêuticas no câncer", disse Bullman.