DID YOU FLOSS TODAY? INVOLVEMENT OF FUSOBACTERIUM NUCLEATUM IN COLON CANCER

Jawad Abed ¹ Johanna E.M. Emgård ¹ Gideon Almogy ² Mouhammad Faroja ² Gideon Zamir ² Ofer Mandelboim ³ Gur Chamutal ³ Gilad Bachrach ¹

¹The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
²Department of General Surgery, The Hadassah-Hebrew University Medical Center, Jerusalem, Israel
³The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jersalem, Israel

Fusobacterium nucleatum is an oral anaerobe that is associated with colorectal adenocarcinoma (CRC). To date, the mechanisms underlying fusobacteria localization to CRC have been unclear. We observed that once in the bloodstream, F. nucleatum rapidly reached colorectal tumors in mice. Colonic tissue localization was tumor-dependent, as fusobacteria did not localize to the colons of tumor-free mice. F. nucleatum CRC localization was mediated by attachment of Fap2, a fusobacterial lectin, to Gal-GalNAc which is overexpressed in both mouse and human CRC. Once in the tumor F. nucleatum inhibits tumor killing by Natural Killer cells and by Tumor Infiltrating Lymphocytes (TILs). The killing-inhibition by F. nucleatum is transmitted by human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cell subsets. TIGIT repression is activated by the fusobacterial Fap2. Our findings suggest that targeting Fap2, host epithelial Gal-GalNAc or TIGIT may provide a means to block F. nucleatum potentiation of CRC.