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The impact of microbiome in immunotherapy for breast cancer
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O cancro da mama é um dos cancros mais comuns em todo o mundo, sendo a principal causa de morte por cancro nas mulheres. Neste contexto, a imunoterapia baseada em inibidores dos checkpoints imunitários surgiu recentemente como um tratamento promissor, particularmente para o cancro da mama triplo-negativo. Contudo, a resposta a esta terapia varia significativamente entre doentes devido às diferenças entre os vários microambientes tumorais. Neste âmbito, o microbioma humano, nomeadamente as bactérias intestinais, parece desempenhar um papel fundamental nesta variabilidade. A microbiota intestinal, influenciada pela genética e pelo tipo de dieta, exerce um papel importante na saúde devido ao seu forte impacto no sistema imunitário, na inflamação e no metabolismo. No entanto, a disbiose intestinal, marcada pela perda de diversidade microbiana e de bactérias benéficas, desregula estes processos e está associada a várias doenças. Investigação recente tem realçado uma interação bidirecional entre a microbiota intestinal e o cancro da mama, bem como as suas terapias. A evidência indica que a microbiota intestinal pode ter tanto efeitos benéficos como prejudiciais no contexto desta doença. Certas espécies bacterianas podem desempenhar um papel positivo através da ativação da resposta imunitária antitumoral, por meio do recrutamento de linfócitos T citotóxicos para o microambiente tumoral, ou pela produção de metabolitos com propriedades protetoras que chegam ao tecido mamário. Em contrapartida, outras bactérias podem desempenhar um papel negativo, ao promover a imunossupressão, e a recaptação de estrogénios livres para a circulação. A própria microbiota da mama também parece estar associada ao cancro da mama por mecanismos semelhantes. A composição da microbiota intestinal e da mama difere nos doentes com cancro da mama em comparação com indivíduos saudáveis, o que reforça o papel potencial da disbiose na progressão desta doença. Além disto, a composição da microbiota influencia a eficácia e a toxicidade da imunoterapia, sendo que uma microbiota equilibrada e estirpes bacterianas específicas estão associadas a melhores resultados do tratamento. A análise da composição da microbiota pode ser útil para prever a resposta à imunoterapia. Intervenções baseadas no microbioma, incluindo o transplante de microbiota fecal, probióticos, intervenção dietética e prebióticos, representam uma abordagem promissora para otimizar as respostas à imunoterapia em doentes com cancro da mama. Contudo, é essencial mais investigação de modo a possibilitar futuras aplicações clínicas.
Breast cancer is one of the most common cancers worldwide, being the leading cause of cancer-related death in women. In this context, immune checkpoint inhibitors-based immunotherapy has recently emerged as a promising treatment, particularly for triple-negative breast cancer. However, the response to this therapy varies significantly among patients due to differences in the various tumor microenvironments. Thus, the human microbiome, namely gut bacteria, appears to play a key role in this variability. The gut microbiota, influenced by genetics and type of diet, plays an important role in health due to its strong impact on the immune system, inflammation and metabolism. However, gut dysbiosis, marked by a loss of microbial diversity and beneficial bacteria, disrupts these processes and it is associated to various diseases. Recent research has highlighted a bidirectional interaction between gut microbiota and breast cancer, as well as its therapies.Evidence indicates that gut microbiota can have both beneficial and harmful effects in the context of this disease. Certain bacterial species can play a positive role by activating antitumor immune response, by recruiting cytotoxic T cells to the tumor microenvironment, or by producing metabolites with protective properties that reach the breast tissue. In contrast, other bacteria may play a negative role by promoting immunosuppression, and the reuptake of free estrogens to circulation. Breast microbiota itself also appears to be associated with breast cancer through similar mechanisms. The composition of both breast and gut microbiota differs in breast cancer patients compared to healthy individuals, which reinforces the potential role of dysbiosis in the progression of this disease. Moreover, microbiota composition influences the efficacy and toxicity of immunotherapy, with a balanced microbiota and specific bacterial strains being associated to improved treatment outcomes. Microbiota composition analysis can be useful to predict the response to immunotherapy. Microbiome-based interventions, including fecal microbiota transplantation, probiotics, dietary intervention and prebiotics, represent a promising approach to optimize immunotherapy responses in breast cancer patients. Nevertheless, further research is essential to enable future clinical applications.
Breast cancer is one of the most common cancers worldwide, being the leading cause of cancer-related death in women. In this context, immune checkpoint inhibitors-based immunotherapy has recently emerged as a promising treatment, particularly for triple-negative breast cancer. However, the response to this therapy varies significantly among patients due to differences in the various tumor microenvironments. Thus, the human microbiome, namely gut bacteria, appears to play a key role in this variability. The gut microbiota, influenced by genetics and type of diet, plays an important role in health due to its strong impact on the immune system, inflammation and metabolism. However, gut dysbiosis, marked by a loss of microbial diversity and beneficial bacteria, disrupts these processes and it is associated to various diseases. Recent research has highlighted a bidirectional interaction between gut microbiota and breast cancer, as well as its therapies.Evidence indicates that gut microbiota can have both beneficial and harmful effects in the context of this disease. Certain bacterial species can play a positive role by activating antitumor immune response, by recruiting cytotoxic T cells to the tumor microenvironment, or by producing metabolites with protective properties that reach the breast tissue. In contrast, other bacteria may play a negative role by promoting immunosuppression, and the reuptake of free estrogens to circulation. Breast microbiota itself also appears to be associated with breast cancer through similar mechanisms. The composition of both breast and gut microbiota differs in breast cancer patients compared to healthy individuals, which reinforces the potential role of dysbiosis in the progression of this disease. Moreover, microbiota composition influences the efficacy and toxicity of immunotherapy, with a balanced microbiota and specific bacterial strains being associated to improved treatment outcomes. Microbiota composition analysis can be useful to predict the response to immunotherapy. Microbiome-based interventions, including fecal microbiota transplantation, probiotics, dietary intervention and prebiotics, represent a promising approach to optimize immunotherapy responses in breast cancer patients. Nevertheless, further research is essential to enable future clinical applications.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Breast cancer Immunotherapy Gut microbiota Breast microbiota Microbiomebased interventions Mestrado Integrado - 2024