Roles of Metabolism, Immunity, and Microbiome in the Pathophysiology of the Breast Cancer Microenvironment

This Research Topic aims to provide an overview and update on the incompletely understood and often controversial aspects of metabolism, immunity, and microbiome in the breast tumor microenvironment (TME). The TME is an essential regulator of breast carcinogenesis and cancer progression. Key players in the TME include tumor-associated immune cells, which are primarily characterized by their immunosuppressive phenotypes. The pro-tumor and immune-suppressive metabolism of TME further regulates the functions of these tumor-associated immune cells. Tumor cells often switch their preferential metabolic activity from oxidative phosphorylation to glycolysis to gain a growth advantage in hypoxic conditions. Such metabolic reprogramming is especially noticeable during breast cancer metastases, and it can result in profound impacts on the interaction between tumor cells and the TME. Different stromal components of the TME, including fibroblasts, fat tissues, and blood vessels, also undergo metabolic changes to assist the establishment of an immune suppressive TME, resulting in tumor growth and metastasis. Furthermore, recent studies have unveiled the roles of the microbiome in regulating breast carcinogenesis. Cancer patients exhibit a microbiome that not only significantly diverges from that of healthy individuals but also demonstrates ‘dysbiosis’ - an imbalance in microbial communities and distinct microbial profiles and compositions. Furthermore, finding evidence of intracellular bacteria in tumors and microbial profiles specific to tumor subtypes and stages has added to the intricacy of the microbiome's regulation of tumor pathophysiology. Comparative studies of the microbiome in breast tumors versus other anatomical sites, such as the colon, may also provide insight into site-specific versus shared microbial influences on tumor biology, progression, and therapeutic response.
The challenges in this field include developing treatments that can overcome immune escape mechanisms within the TME. Immunotherapy, especially immune checkpoint inhibitors, has shown limited success in breast cancer compared to other solid tumors. Employing transcriptomic and bioinformatic tools for precision medicine, exploring epigenetic, signalling pathway, and immune-based therapies may enhance treatment options. Although certain bacteria show promise in early detection studies, the complexity of the microbiome, including functional redundancy and ecological shifts, complicates our understanding of its role in carcinogenesis. A definitive microbial profile as a reliable biomarker for breast cancer remains elusive due to inconsistent findings.
Sub Topics - some of the suggested topics include, but are not limited to:
- Specific metabolic pathways used by both tumor and immune cells within the breast TME and their influences on immune cell activity and tumor progression.
- Mechanisms by which the microbiome regulates immune responses within the breast TME and the impacts on breast cancer progression.
- Innovative therapeutics targeted to tumor-associated metabolism, immunity, and/or microbiome.
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- Hypothesis and Theory
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