Symbiotic bacteria can be found living in and on the majority of our body’s surfaces, with 99 percent of these micro-interlopers inhabiting the human gastrointestinal tract. These intestinal microbes are referred to as the gut microbiota, and are crucial in the regulation of the immune system, as well as aiding in the development of cancer. Specifically, evidence suggests the gut microbiota is instrumental in the production of colorectal cancer tumors, aided by the bacterium Fusobacterium nucleatum (Fn). The Fn microbial species is thought to increase the level of a type of immune cell known as a myeloid cell, implicated in the suppression of other white blood cells, to hamper the host’s anticancer immune response. Now, a study from researchers at Wuhan University develops a hybrid bacteriophage or phage capable of modulating the gut microbiota to suppress colorectal cancer growth. The team states they selected the M13 phage species due to its propensity for binding to Fn, coating the phage in silver to successfully block immunosuppression in the tumor microenvironment (TME). The opensource study is published in the journal of Science Advances.
Previous studies show symbionts contained within our gastrointestinal system have profound antitumor effects whilst modulating the host immune system. In contrast, this gut bacteria can also promote tumor growth, as well as inhibiting cancer treatment, with this precipitously balanced microbial community proving vulnerable even to antibiotic treatment. Recent studies have linked the development of colorectal cancer development to the gut microbiota, particularly where the presence of Fn is detected in cancerous colorectal tissue. It is thought this individual species of bacteria recruits more myeloid cells into diseased tissue resulting in an immune-suppressed TME, further dampening T cell response. This information taken together points to a naturally-based treatment able to manipulate specific gut bacteria to boost antitumor effects. The current study augments a species of bacteriophage, a naturally-occurring virus possessing the ability to target and kill specific bacteria, assisted by nanomaterials to boost its antitumor effects.
The current study utilizes a bacteriophage display library to identify a species capable of binding Fn bacteria, called the M13 phage. Silver nanoparticles were then assembled electrostatically on the surface of the M13 phage’s capsid protein to achieve specific clearance of Fn and remodel the TME. Results show once the hybrid M13 phages accumulated in the TME they selectively killed protumor Fn and blocked the recruitment of immunosuppressant myeloid cells. Data findings show in mice, the hybrid phages also target Fn in the gut all the while reducing myeloid cell migration to the tumor site.
The lab states, in addition, their augmented bacteriophage promotes the activation of antigen-presenting cells to boost the immune system for colorectal cancer suppression. They go on to add it was demonstrated the hybrid phage boosted the host immune response, delayed the progression of colorectal cancer, and prolonged the survival of mice. However, they stress if there is no specific colonization of Fn in the tumor it is unlikely this pseudo-natural cancer therapy will work.
The team surmises they develop a new type of immunotherapy targeting colorectal cancer, capable of regulating the gut microbiota to reverse immunosuppressive TME through the augmentation of phages. For the future, the researchers state their work hints at the possibility of selectively modulating individual microbiota species using phages also capable of boosting immunity to dampen the progression of colorectal cancer.
Source: Wuhan University
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