Two studies reveal how bacteria infiltrate tumors and could help tumors progress and spread. A team of researchers at the Fred Hutchinson Cancer Center in Seattle, USA, have also identified that different microbial players in a tumor’s microbiome could influence how the cancer responds to treatment.
The findings also suggest a link between oral health and cancer, since bacteria present in the mouth are associated with cancers in other parts of the body. The two articles, published in “Cell Reports” and “Nature”, focus on an oral bacterium called Fusobacterium nucleatum, which has been linked to colorectal cancer.
Most cancers have outside help in their efforts to survive and grow. Non-tumor cells surrounding a tumor can help it fend off attacks by the immune system, resist therapies that attack it, and allow it to spread to other parts of the body. Researchers are now discovering that some of these helpful neighbors aren’t even human cells, they’re bacteria.
“We have seen that there are regions of the tumor that are colonized by bacteria and differ functionally from regions that do not harbor bacteria,” says Susan Bullman, author of the study in “Nature.” “And these bacteria-rich regions have higher metastatic potential.”
Together with molecular microbiologist Christopher, Bullman showed that F. nucleatum can shape the conditions in tumors to keep them safe from immunological attack and help them spread throughout the body. What’s more, they discovered that some cancer therapies may work because they target not only tumor cells, but also the bacteria that help them.
The team also found that other bacteria, including Escherichia coli, can render an antimicrobial and chemotherapeutic drug ineffective, potentially protecting both the tumor and F. nucleatum from treatment. These findings could help develop new strategies to treat or attack cancer by targeting its microbiome.
The existence of an association between colorectal cancer and bacteria may seem logical; however, there are other tumors, such as breast, pancreatic, and lung, that harbor microbial communities, and studies show that tumor microbiomes can shape tumor development, progression, and response to treatment.
Using cutting-edge technology that allows researchers to detect where genes are turned on and off in slices of tumor tissue (spatial transcription), a variety of bacterial species were found to live inside oral and colorectal cancers, but not to spread in the same way.
The study may help explain how a patient’s microbiota might influence whether their cancer responds to a checkpoint inhibitor.
Regions colonized by bacteria were highly immunosuppressive and had fewer T cells, designed to kill cancer, than other areas. Areas that had T cells near the bacteria also had upregulation of immune checkpoint proteins, which restrict the cancer-killing effects of T cells. Several checkpoint inhibitor drugs are approved for use in colorectal cancer, and this study may help explain how a patient’s microbiota might influence whether their cancer responds to a checkpoint inhibitor.
The study also shows that bacteria-infected tumor cells promoted genes associated with cancer progression and metastasis. In the oral tumor samples, the researchers found that the bacteria preferentially infected cancer epithelial cells and specific immune cells within the patients’ tumors.
Microbes traditionally associated with oral inflammatory disease may be linked to extraoral and gastrointestinal cancers
“It is possible that microbes traditionally associated with oral inflammatory disease are associated with extraoral and gastrointestinal cancers, pointing to the oral cavity as a breeding ground for pathogenic oncomicrobials,” Johnston says.
In addition to allowing pathogens to spread to new areas of the body, it is possible that inflammation in the mouth, in the form of periodontal or endodontic disease, may be selecting for and encouraging the growth of bacteria that are more specialized to grow in harsh conditions. conditions and able to evade immune attack, he explains.
“This holistic approach to assessing the tumor microenvironment, which is a multispecies ecosystem, will enhance our understanding of cancer biology and I believe will reveal new therapeutic vulnerabilities in cancer,” Bullman adds.