What is already known on this topic
The gut microbiota seems to influence how well some cancer drugs work, but particular bacteria such as Fusobacterium nucleatum could also promote tumor growth.
What this research adds
Researchers developed a tool to modulate the gut microbiota and neutralize the tumor-promoting microenvironment. The tool, which combines antibacterial nanomaterials with viruses that only infect Fusobacterium nucleatum, reversed the immunosuppressive tumor microenvironment and enhanced immunotherapy response in mice.
The findings could open up new avenues for the treatment of colorectal cancer.
The gut microbiota seems to influence how well some cancer drugs work, but particular bacteria could also promote tumor growth. Now researchers developed a tool to modulate the gut microbiota for neutralizing the tumor-promoting microenvironment.
The findings, published in Science Advances, could open up new avenues for the treatment of colorectal cancer.
Recent studies have shown that colorectal cancer is associated with gut bacteria, and that the microbe Fusobacterium nucleatum (Fn) can create an immune-suppressive tumor microenvironment that further promotes tumor growth.
Cancer treatment with antibiotics has shown therapeutic potential for inhibiting cancer proliferation. However, because of the multiple effects of gut microbiota, the use of antibiotics as a way to modulate specific gut bacteria is limited, as antibiotics would remove bacteria that have a positive effect on cancer treatment as well as those that promote tumor development.
So a team of researchers led by Xian-Zheng Zhang at Wuhan University devised a way to manipulate the microbiota without antibiotics by combining antibacterial nanomaterials with viruses that only infect Fn.
First, the researchers investigated the role of Fn within the tumor-immune microenvironment in mice. They found that rodents with Fn in their colorectal tumors had high levels of particular immune cells that expand in pathological situations such as chronic infections and cancer. Removing Fn reduced the expansion of these immune cells and reversed the immunosuppressive tumor microenvironment, thus enhancing immunotherapy response.
Next, the researchers screened a panel of viruses that infect only bacteria, known as bacteriophages or phages, to find a virus that could infect specifically Fn. The team also looked for antibacterial materials that could help Fn-specific phages to kill Fn. They found that silver nanoparticles, which are widely used in the medical field and consumer products as antibacterial agents, could effectively kill Fn. Finally, the researchers assembled the silver nanoparticles on the surface of the phages.
In cells grown in a laboratory dish, the silver nanoparticles combined with the phages were able to kill Fn and induce the activation of immune cells, boosting the antitumor immune response.
Treating mice with the phage-silver nanoparticles mix together with widely used anticancer drugs reduced tumor growth, eliminated the immunosuppressive microenvironment, and prolonged the survival of the animals. The phages also activated antigen-presenting cells that further increased the host immune response for colorectal cancer suppression.
The researchers caution that, although promising, such treatment could have only a minimal therapeutic effect on colorectal cancer if there is no specific colonization of Fn in the tumor. They also add that more work on the combination of antibacterial nanomaterials with phages is needed to enhance the therapeutic effect on colorectal cancer. “We expect that new efforts targeting specific tumor microbiota for tumor therapy will become an increasingly researched field in both basic and translational research,” they say.