Fusobacterium nucleatum subsp. nucleatum RadD binds Siglec-7 and inhibits NK cell-mediated cancer cell killing
Johanna Galaski,
Ahmed Rishiq,
Mingdong Liu,
Reem Bsoul,
Almog Bergson,
Renate Lux,
Gilad Bachrach,
Ofer Mandelboim
Affiliations
Johanna Galaski
The Concern Foundation Laboratories at the Lautenberg Center for General and Tumor Immunology, Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Faculty of Medicine, The Hebrew University Medical School, Jerusalem, Israel; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Medical Microbiology and Hygiene, Medical Centre University of Freiburg, Freiburg, Germany
Ahmed Rishiq
The Concern Foundation Laboratories at the Lautenberg Center for General and Tumor Immunology, Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Faculty of Medicine, The Hebrew University Medical School, Jerusalem, Israel
Mingdong Liu
The Concern Foundation Laboratories at the Lautenberg Center for General and Tumor Immunology, Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Faculty of Medicine, The Hebrew University Medical School, Jerusalem, Israel
Reem Bsoul
The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
Almog Bergson
The Concern Foundation Laboratories at the Lautenberg Center for General and Tumor Immunology, Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Faculty of Medicine, The Hebrew University Medical School, Jerusalem, Israel
Renate Lux
Section of Periodontics, Division of Constitutive & Regenerative Sciences, UCLA School of Dentistry, Los Angeles, CA 90095, USA
Gilad Bachrach
The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
Ofer Mandelboim
The Concern Foundation Laboratories at the Lautenberg Center for General and Tumor Immunology, Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Faculty of Medicine, The Hebrew University Medical School, Jerusalem, Israel; Corresponding author
Summary: Fusobacterium nucleatum is an oral commensal bacterium that can colonize extraoral tumor entities, such as colorectal cancer and breast cancer. Recent studies revealed its ability to modulate the immune response in the tumor microenvironment (TME), promoting cancer progression and metastasis. Importantly, F. nucleatum subsp. animalis was shown to bind to Siglec-7 via lipopolysaccharides, leading to a pro-inflammatory profile in human monocyte-derived dendritic cells. In this study, we show that F. nucleatum subsp. nucleatum RadD binds to Siglec-7 on NK cells, thereby inhibiting NK cell-mediated cancer cell killing. We demonstrate that this binding is dependent on arginine residue R124 in Siglec-7. Finally, we determine that this binding is independent of the known interaction of RadD with IgA. Taken together, our findings elucidate the targeting of Siglec-7 by F. nucleatum subsp. nucleatum RadD as a means to modulate the NK cell response and potentially promoting immune evasion and tumor progression.
