TY - JOUR
T1 - Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance
AU - Jandus, Camilla
AU - Boligan, Kayluz Frias
AU - Chijioke, Obinna
AU - Liu, He
AU - Dahlhaus, Meike
AU - Démoulins, Thomas
AU - Schneider, Christoph
AU - Wehrli, Marc
AU - Hunger, Robert E.
AU - Baerlocher, Gabriela M.
AU - Simon, Hans Uwe
AU - Romero, Pedro
AU - Münz, Christian
AU - Von Gunten, Stephan
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84897566999&partnerID=8YFLogxK
U2 - 10.1172/JCI65899
DO - 10.1172/JCI65899
M3 - Article
C2 - 24569453
AN - SCOPUS:84897566999
SN - 0021-9738
VL - 124
SP - 1810
EP - 1820
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 4
ER -