Fusobacterium Effects on Oral Cancer Progression and the Tumor Immune Microenvironment
Oral cavity squamous cell carcinoma (OCSCC) is a very aggressive and deadly disease with poor survival rates following standard treatment. A characteristic of OCSCC is that the immune cells within the tumor microenvironment (or TIME) are often suppressed allowing the cancer to hide from or “evade” the patient’s immune system. The immunosuppressive TIME is a major barrier of response to traditional and immune based therapies. There is a critical need to understand the TIME and the factors that contribute to OCSCC progression and treatment resistance.
The oral microbiome has been linked to many diseases including oral cancer. Our group demonstrated that oral Fusobacterium is; much more abundant in OCSCC samples when compared to normal tissues, can influence immune regulatory molecules (immune checkpoints) in oral cancer cells, and may play a direct role in assisting cancers to evade the immune system.
We seek to understand how Fusobacterium can influence OCSCC through direct cellular interactions, and by influencing the TIME. In Aim 1, we will infect oral cancer cells with Fusobacterium (and bacterial components) and measure the effect on immune checkpoints and associated genetic pathways. In Aim 2 we will utilize a mouse model of OCSCC to study the effects of Fusobacterium infection on tumor growth and immunosuppressive cell infiltration. The PI of this proposal is both a translational researcher and a head and neck cancer surgeon, and she will use the results from this to inform future clinical trial design targeting bacteria for therapeutic benefit.
The goal of my study is to help us identify how specific bacteria can affect cancer cell development in the oral cavity. We hope to target this bacteria in order to create new therapies in the future.