Certain Bacteria Help Cancerous Tumors Resist Treatment

Many cells play a role in cancer’s spread throughout the body, not just malignant ones. Fusobacterium nucleatum is one such species, with previous research linking this oral bacterium to colorectal cancer. Many of the inner workings of bacteria’s influence on tumor microenvironments have remained poorly understood, so researchers at the Fred Hutchison Cancer Center in Seattle decided to investigate the links between these microbial players and cancer’s spread.

The team published two papers on the bacterium, one in Cell Reports and the other in Nature, but had similar goals for each. “What we’re showing is that there are regions of the tumor that are heavily colonized by bacteria — micro-niche regions — and they differ functionally from regions that do not harbor bacteria,” says Susan Bullman, Fred Hutch cancer microbiome researcher and study co-lead, referring to the work outlined in the Nature study. “And these bacteria-rich regions have increased metastatic potential.”

Bullman and colleague Christopher D. Johnston, Ph.D., combined observations from tumors with lab-based experiments and small-molecule drug screenings to show that F. nucleatum helps tumors spread throughout the body, as well as protects against immune responses. This provided a possible explanation as to why some cancer therapeutics aren’t as effective – because they only target the tumor cells, not the bacteria that assist them.

The team also identified other microbes, including E. coli, that may render anti-microbial and chemotherapeutic drugs less effective and protect F. nucleatum from immunotherapeutic interventions. “This work is at the intersection of cancer and microbiome research,” states Bullman. “There’s compelling emerging data to suggest that nearly all major cancer types harbor an intra-tumoral microbiota.”

The two studies resulted in numerous findings. For example, in the lab, the researchers grew colorectal cancer spheroids with neutrophils to reduce T-cell migration and invasion. The neutrophils spread through spheroids without bacteria but migrated towards the spheroid’s center, eventually becoming trapped – a potential explanation for why there are so few T cells in regions colonized by bacteria.

Johnston notes that, in addition to allowing pathogens to spread to new areas of the body, it’s possible that inflammation in the mouth, like that occurring with periodontal or endodontic diseases, could encourage the growth of bacteria more specialized for replication in adverse conditions.

“There is a trend emerging of microbes that are traditionally associated with oral inflammatory disease being found in association with extra-oral and gastrointestinal cancers — which highlights the oral cavity as a breeding ground for pathogenic onco-microbes,” says Johnston.

For future work, the team wants to explore how to make tumors more responsive to immunotherapy or chemotherapy by directly manipulating the microbiome. They hope to design microbiome-modulating therapeutics to prevent and treat cancer more effectively.

“This holistic approach to assessing the tumor microenvironment, which is a multi-species ecosystem, will advance our understanding of cancer biology, and I believe will reveal new therapeutic vulnerabilities in cancer,” states Bullman.