Takeshi Morinaga, Masaaki Iwatsuki, Kohei Yamashita, Noriko Yasuda-Yoshihara, Taishi Yamane, Chihiro Matsumoto, Kazuto Harada, Kojiro Eto, Junji Kurashige, Takatsugu Ishimoto, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba
Annals of surgical oncology 2023 FebSome 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. 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. 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. 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. © 2022. Society of Surgical Oncology.
Takeshi Morinaga, Masaaki Iwatsuki, Kohei Yamashita, Noriko Yasuda-Yoshihara, Taishi Yamane, Chihiro Matsumoto, Kazuto Harada, Kojiro Eto, Junji Kurashige, Takatsugu Ishimoto, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. Dynamic Alteration in HLA-E Expression and Soluble HLA-E via Interaction with Natural Killer Cells in Gastric Cancer. Annals of surgical oncology. 2023 Feb;30(2):1240-1252
PMID: 36149610
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