Fusobacterium nucleatum supresses anti-tumor immunity by activating CEACAM1

Chamutal Gur; Naseem Maalouf; Amjad Shhadeh; Orit Berhani; Bernhard B Singer; Gilad Bachrach; Ofer Mandelboim

doi:10.1080/2162402X.2019.1581531

Fusobacterium nucleatum supresses anti-tumor immunity by activating CEACAM1

Oncoimmunology. 2019 Mar 27;8(6):e1581531. doi: 10.1080/2162402X.2019.1581531. eCollection 2019.

Authors

Chamutal Gur¹, Naseem Maalouf², Amjad Shhadeh², Orit Berhani¹, Bernhard B Singer³, Gilad Bachrach², Ofer Mandelboim¹

Affiliations

¹ The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, Institute for Medical Research Israel-Canada (IMRIC), Jerusalem, Israel.
² The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel.
³ Institut für Anatomie, Universitätsklinikum Essen, Essen, Germany.

Abstract

Fusobacterium nucleatum (F. nucleatum) is an oral anaerobe found to be enriched in colorectal cancer (CRC). Presence of F. nucleatum in CRC has been correlated with resistance to chemotherapy and poor prognosis. We previously demonstrated that the Fap2 outer-surface protein of F. nucleatum binds and activates the human inhibitory receptor TIGIT which is expressed by T and Natural Killer (NK) cells, and inhibits anti-tumor immunity. Here we show that F. nucleatum also binds and activates the human inhibitory receptor CEACAM1 leading to inhibition of T and NK cells activities. Our results suggest that using CEACAM1 and TIGIT inhibitors and specific targeting of fusobacteria should be considered for treating fusobacteria-colonized tumors.

Keywords: CEACAM1; Fusobacterium nucleatum; inhibition of killing.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

This work was supported by the Israel Cancer Research Fund Project grant and the Israel Science Foundation grant 201/15 to G.B. Further support came from the Israel-China Science Foundation, the GIF foundation, the ICRF professorship grant, the Helmholtz Israel grant and the Marry Curie grant (all to O.M.). Additional support came from the ISF Moked grant and the Ministry of Science and Technology to O.M and G.B.