Challenges in investigating immune-microbiome interactions in breast cancer

The impact of the human microbiome, the diverse collection of microorganisms that inhabit nearly every niche in the human body, in shaping the immune response to dysbiotic events is apparent if poorly understood, particularly in complex, evolving disease states such as breast cancer. The impacts can be both indirect via metabolites and immune-interactions along the skin, gut, and oral cavities where the microbial communities are most abundant, or direct in the tumor microenvironment where microbial activities can promote growth or clearance of cancerous cells. Based on reports of using gut microbial signatures to predict therapeutic efficacy, the role that gut microbes and their metabolites may play in shaping the success or failure of immunotherapy has been extensively reviewed. In this review, we dissect the evidence for the direct and distal impact of microbes on oncogenesis, tumor growth and the immune responses to combat or promote tolerance of breast cancer tumors. Implementation of robust, valid analyses and methods are lacking in the field, and we provide recommendations for researchers and clinicians to work together to characterize the micro-biome-immune-breast cancer interactions that will hopefully enable the next generation of biomarkers and targets for improving disease outcomes.