Aberrant glycosylation actively contributes to
tumor progression and is a key hallmark of
cancer. Most of the
glycan moieties expressed on the surface of
cancer cells are
sialic acids that may modulate antitumor immune responses via binding to
sialic acid-binding immunoglobulin-like lectins (
Siglecs) expressed by immune cells. Here we show that
Siglecs may decrease the
bladder tumor immune response mediated by natural killer (NK) cells. We observed higher NK cell activity against desialylated
bladder tumor cell lines. We therefore determined the expression of nine
Siglecs on circulatory NK cells from healthy donors and patients with
bladder cancer (BCa). NK cells from blood mainly express Siglec-7, which is highly upregulated in non-muscle-invasive BCa (
NMIBC), as well as Siglec-6, albeit at a much lower level. However, both
Siglecs are expressed by urinary NK cells from
NMIBC patients undergoing bacillus Calmette-Guérin
therapy. Ex vivo analysis of Siglec-6 and Siglec-7 expression levels on
tumor-infiltrating NK cells (TINKs) from BCa patients showed that only Siglec-7 is expressed by TINKs. Finally, analyses for The
Cancer Genome Atlas data set revealed that BCa patients with high expression levels of Siglec-7 have a poor survival rate. This work indicates that Siglec-7 may restrain NK-mediated antitumor immunity in BCa.
PATIENT SUMMARY: We investigated the expression of
proteins called
Siglecs in natural killer (NK) cells from patients with
bladder cancer. We showed that levels of the
protein Siglec-7 in blood, urine, and
tumors from patients with
bladder cancer are associated with poor clinical outcomes. Thus, Siglec-7 may be involved in the regulation of antitumor immunity mediated by NK cells in
bladder cancer.