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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number110157
JournaliScience
Volume27
Issue number6
DOIs
StatePublished - 21 Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

  • cancer
  • immunology
  • microbiology
  • molecular biology

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