Cancer Cell Lewis X Plays a Minor Role in NK Cell Immune Evasion

Production of aberrant glycans by cancer cells constitutes a key immunosuppressive strategy to avoid destruction by immune cells. Although sialic acid-containing glycans are known to dampen the activation of lymphocytes, including Natural Killer (NK) cells, the role of fucose-containing glycans remains poorly characterized. In this work, we explored the role of Lewis X (LeX) in cancer cell-NK cell interactions. We induced ectopic expression of FUT9, an 1-3/4-fucosyltransferase, in two colorectal cancer cell lines and showed this enzyme only synthesized LeX structures but not sialyl-LeX. FUT9 introduction was not associated with altered MHC class I surface expression, nor with CD2 (which has been proposed as a receptor for LeX) binding to cancer cells. By inhibiting fucosylation we could demonstrate that CD2 binding was furthermore independent of surface fucosylated glycans in three independent cell lines. Lastly, FUT9/LeX had a limited role in cancer cell destruction and expression of activation markers by NK cells. Overall, our study suggests that, unlike sialylated glycans, 1-3/4-fucosylated glycans have limited impact on cancer cell evasion of NK cell-mediated destruction.