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.
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