Bacteria in metastases: The microbiome of cancer
Within our bodies, microbes have developed an essential, commensal role and are found in many niches. A comprehensive study, recently published in Cell, provides a fascinating insight into the role of microbes in cancer and how they can modulate prognosis and responses to treatment.
The research, published in Cell, was led by Emile Voest and Lodewyk Wessels at the Netherlands Cancer Institute in Amsterdam. The researchers analysed over 4000 tumors seeking to understand the diversity of microbes and the ways they interact with cancer cells and the tumor microenvironment.
The human adult has some 30-40 trillion cells. Similarly, the human microbiome contains nearly 40 trillion microorganisms (97% in the GI tract) across 3000 species. The importance of bacteria in cancer aetiology and response to drugs is well established. Gut bacteria, for example, are able to metabolize drugs and influence the effectiveness of immunotherapy and chemotherapy. Some species of bacteria have been linked to a poor response to immunotherapy. Faecal transplants from patients who respond well to treatment can improve outcomes in poor responders.
Given the key roles of gut bacteria in responding to treatment and the way tissue is modulated by microbes (e.g. Helicobacter pylori), there is a good possibility that understanding the bacteria resident within the tumours will yield important insights.
The Dutch study of over 4000 tumours allows for the generation of large data sets and subsequent powerful statistical analysis to better understand how bacteria help or hinder cancer and modulate cancer therapy.
The researchers were particularly interested in metastatic cancer, examining tissue across 26 types of cancer. Their approach was sequence-based, performing comprehensive sequencing of the cancer DNA samples which allowed them to identify bacteria as well as generate information on the cancer cells themselves. The researchers catalogued 165 genera (different types) of bacteria in 3,526 of the 4164 samples analysed.
What is the origin of the bacteria? The bacteria in metastases could have travelled with cancer cells in the blood from the primary cancer site. However, the data analysis showed the largest correlation between the type of bacteria and the tissue which provided the metastatic niche.
There was also a correlation between the presence of bacteria and prognosis. For example, lung cancer patients with Fusobacterium in their metastasis responded worse to immunotherapy than peers without that particular bacteria.
Interestingly, the research uncovered an association between the immune response to a tumor and bacterial load. The groups also found a correlation between the aggressiveness of a tumor and the diversity of their bacterial colonisers. In general, the more diverse the bacteria, the more active the tumor cells were.
This study opens up the possibility of targeting certain bacteria therapeutically to improve outcomes in cancer treatment.
IMAGE Bacteria graphic CREDIT: Bigstock
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