RRC ID 78177
Author Morinaga T, Iwatsuki M, Yamashita K, Yasuda-Yoshihara N, Yamane T, Matsumoto C, Harada K, Eto K, Kurashige J, Ishimoto T, Baba Y, Miyamoto Y, Yoshida N, Baba H.
Title Dynamic Alteration in HLA-E Expression and Soluble HLA-E via Interaction with Natural Killer Cells in Gastric Cancer.
Journal Ann Surg Oncol
Abstract 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.
Volume 30(2)
Pages 1240-1252
Published 2023-2-1
DOI 10.1245/s10434-022-12505-0
PII 10.1245/s10434-022-12505-0
PMID 36149610
MeSH Culture Media, Conditioned / metabolism HLA Antigens / metabolism HLA-E Antigens Histocompatibility Antigens Class I Humans Killer Cells, Natural Stomach Neoplasms* / metabolism
Human and Animal Cells Kato III(RCB2088)