Tumor acceleration by Fusobacterium nucleatum

Amjad Shehadeh ¹ Naseem Maalouf ¹ Tamar Alon ¹ Lishay Parhi ¹ Jawad Abed ¹ Liat Dassa ² Chamutal Gur ² Ofer Mandelboim ² Bachrach Gilad ¹

¹The Institute of Dental Sciences, The Hebrew University – Hadassah School of Dental Medicine, Israel
²The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, Institute for Medical Research Israel-Canada (Imric), Israel

Fusobacterium nucleatum is an oral anaerobe involved in the development of periodontal disease. Involvement of F. nucleatum was recently found in colon cancer where it is associated with poor prognosis. We found that oral fusobacteria can reach colon cancer via the blood circulation. Hematogenous fusobacteria utilize their Fap2 lectin to bind Gal-GalNAc over-displayed by colon cancer to colonize the tumor. Gal-GalNAc is highly-displayed in additional tumors where fusobacterial gDNA can be found.

Once in the tumors, fusobacteria can inhibit anti-tumor immunity by activating the immune cell suppressor receptors TIGIT and CEACAM1, and by degrading immune-cell activating receptors.

As fusobacteria can accelerate tumor development, targeting F. nucleatum might be beneficial during treatment of fusobacteria-colonized tumors.