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Updated: Jun 22, 2025

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
Fusobacterium nucleatum subsp. nucleatum RadD binds Siglec-7 and inhibits NK cell-mediated cancer cell killing
Johanna Galaski1,2,3, Ahmed Rishiq1, Mingdong Liu1
1The 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.
Abstract:
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.
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