Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance

Jandus, Camilla; Frias Boligan, Kayluz; Chijioke, Obinna; Liu, He; Dahlhaus, Meike; Demoulins, Thomas; Schneider, Christoph; Wehrli, Marc; Hunger, Robert E.; Baerlocher, Gabriela M.; Simon, Hans-Uwe; Romero, Pedro; Münz, Christian; von Gunten, Stephan (2014). Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. Journal of clinical investigation, 124(4), pp. 1810-1820. American Society for Clinical Investigation 10.1172/JCI65899

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Abstract Alteration of the surface glycosylation pattern on malignant cells potentially affects tumor immunity by directly influencing interactions with glycan-binding proteins (lectins) on the surface of immunomodulatory cells. The sialic acid-binding Ig-like lectins Siglec-7 and -9 are MHC class I-independent inhibitory receptors on human NK cells that recognize sialic acid-containing carbohydrates. Here, we found that the presence of Siglec-9 defined a subset of cytotoxic NK cells with a mature phenotype and enhanced chemotactic potential. Interestingly, this Siglec-9+ NK cell population was reduced in the peripheral blood of cancer patients. Broad analysis of primary tumor samples revealed that ligands of Siglec-7 and -9 were expressed on human cancer cells of different histological types. Expression of Siglec-7 and -9 ligands was associated with susceptibility of NK cell-sensitive tumor cells and, unexpectedly, of presumably NK cell-resistant tumor cells to NK cell-mediated cytotoxicity. Together, these observations have direct implications for NK cell-based therapies and highlight the requirement to consider both MHC class I haplotype and tumor-specific glycosylation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Frias Boligan, Kayluz; Liu, He; Demoulins, Thomas; Schneider, Christoph; Baerlocher, Gabriela M.; Simon, Hans-Uwe; Münz, Christian and von Gunten, Stephan

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Anita Dähler

Date Deposited:

30 Oct 2014 09:41

Last Modified:

19 Jan 2015 15:22

Publisher DOI:

10.1172/JCI65899

PubMed ID:

24569453

BORIS DOI:

10.7892/boris.59704

URI:

https://boris.unibe.ch/id/eprint/59704

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