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.
Camilla Jandus, Kayluz Frias Boligan, Obinna Chijioke, He Liu, Meike Dahlhaus, Thomas Démoulins, Christoph Schneider, Marc Wehrli, Robert E. Hunger, Gabriela M. Baerlocher, Hans-Uwe Simon, Pedro Romero, Christian Münz, Stephan von Gunten
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.