Bacteria that are commonly found in the mouth are often abundant in patients with colon cancer, but the potential role these microbes play in tumour development has not been clear. An opensource study published in the journal Immunity reveals that the oral pathogen Fusobacterium nucleatum protects a variety of tumour cells from being killed by immune cells. The findings could open new avenues for the treatment of cancer in human patients.
Certain bacteria have previously been shown to fight cancer, so the surprising finding by researchers from The Hebrew University Hadassah Medical School is that bacteria such as Fusobacterium nucleatum can grant tumours an anti-immune defense mechanism. Blocking the interaction between these bacteria and immune cells might improve anti-tumour immunity both in general and with regard to colon cancer in particular.
Immune cells called natural killer cells defend the body against a variety of health threats, including viruses and parasites. These cells can also kill tumours, but cancer cells have evolved ways to evade this immune response. In the early 1890s, a surgeon named William Coley recognized that certain bacteria can enhance anti-tumour immunity, and he even used bacterial extracts to successfully treat cancer patients. But the relationship between bacteria and tumours is complex, and until now, it was not known whether other types of bacteria that are common in cancer patients could have the opposite effect: protecting developing tumours from immune cell attack.
To address this question the team studied how the anti-cancer activity of natural killer cells might be affected by Fusobacterium nucleatum, an oral pathogen that has been linked to periodontal diseases and is also present in human colorectal tumours.
They found that this bacterium protects a variety of human tumour cells from destruction by human natural killer cells. Moreover, this immune evasion depends on the binding of a bacterial protein called Fap2 to an immune cell receptor called TIGIT. The team state that the implications are that if the Fusobacterium nucleatum bacteria is removed from the tumours or TIGIT is inhibited with antibodies, researchers might enable immune cells to kill the colon tumours more efficiently.
The researchers now intend to test whether this bacterium is found in other types of tumours and whether additional bacteria that colonize tumours affect the activity of immune cells. They also plan to study Fap2-TIGIT interactions in more detail and develop ways to block these interactions. Because Fusobacterium nucleatum specifically targets tumours, it may be possible in the future to use a Fap2-deleted Fusobacterium nucleatum to guide therapeutic agents to kill the tumours.