Dynamic Alteration in HLA-E Expression and Soluble HLA-E via Interaction with Natural Killer Cells in Gastric Cancer.

Background: Some reports showed the immune tolerance of soluble human leukocyte antigen E (HLA-E), but the role that soluble HLA-E plays in gastric cancer (GC) is unknown. We aimed to clarify the molecular mechanism and clinical significance of soluble HLA-E in GC.

Methods: We examined the expression of HLA-E on GC cells and soluble HLA-E under co-culture with natural killer (NK) cells in a time-dependent manner. Changes in NK cell activity were investigated using anti-NK group 2 member A (NKG2A) antibodies in the presence of soluble HLA-E. Expression of soluble HLA-E in the serum of GC patients was determined.

Results: Whereas HLA-E expression on GC cells peaked with interferon (IFN)-γ secretion by NK cells in a time-dependent manner, soluble HLA-E was upregulated in conditioned medium. Pre-incubation with anti-NKG2A antibodies increased the activation of NKG2A NK cells in the presence of soluble HLA-E. Expression of soluble HLA-E in the serum of GC patients correlated with disease progression.

Conclusions: HLA-E expression dynamically changes on GC cells and in conditioned medium. Furthermore, soluble HLA-E can contribute to immune escape in GC cell lines, which may have significance in clinical practice. Moreover, soluble HLA-E may be a potential prognostic biomarker.