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Siglec-7/-9 ligands shield tumor cells from NK cell attack
  1. Camilla Jandus1,7,
  2. Kayluz Frias Boligan1,
  3. Obinna Chijioke2,
  4. He Liu1,
  5. Meike Dahlhaus3,4,
  6. Thomas Démoulins5,
  7. Christoph Schneider1,
  8. Marc Wehrli1,
  9. Robert E Hunger6,
  10. Gabriela M Baerlocher3,4,
  11. Hans-Uwe Simon1,
  12. Pedro Romero7,
  13. Christian Münz2 and
  14. Stephan von Gunten1
  1. Aff1 grid.5734.50000000107265157Institute of PharmacologyUniversity of Bern Bern Switzerland
  2. Aff2 grid.7400.30000000419370650Department of Viral Immunobiology, Institute of Experimental ImmunologyUniversity of Zürich Zürich Switzerland
  3. Aff3 grid.411656.10000000404790855Department of HematologyUniversity Hospital of Bern Bern Switzerland
  4. Aff4 grid.5734.50000000107265157Experimental Hematology, Department of Clinical ResearchUniversity of Bern Bern Switzerland
  5. Aff5 grid.5734.50000000107265157Institute of Virology and Immunoprophylaxis Mittelhäusern Switzerland
  6. Aff6 grid.411656.10000000404790855Department of DermatologyUniversity Hospital of Bern Bern Switzerland
  7. Aff7 grid.9851.50000000121654204Translational Tumor Immunology GroupLudwig Center for Cancer Research at the University of Lausanne Lausanne Switzerland

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Meeting abstracts

Altered surface glycosylation on malignant cells may affect tumor immunity by direct interaction with glycan-binding proteins (lectins) on immune cells. Siglec-7 and -9 are MHC class I-independent inhibitory receptors on human NK cells that recognize sialic acid-containing carbohydrates (sialoglycans). We have found that Siglec-7 and -9 ligands are significantly overexpressed on human tumor cell lines of different histological types and in tumor biopsies from melanoma patients. Enzymatic removal of these sialoglycans ligands on tumor cells or interference with blocking monoclonal antibodies (mAbs) to Siglec-7 and -9 conferred in vitro stimulatory NK cell activity (e.g. specific killing, degranulation, cytokine secretion) and considerably greater anti-tumor responses not only to NK cell-sensitive, but also to relatively NK cell non-susceptible tumor cells. In in vivo experiments, in a mouse model with a reconstituted human NK cell compartment, a significant increase in NK cell-mediated cytotoxicity was obtained after removal of sialic acids on the surface of the target tumor cells. The observation that tumor cells use Siglec ligands for shielding against NK-cell attack has direct implications for NK cell-based anti-tumor strategies and for the design of glycan-based cancer therapeutics.