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

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Funding

This work was supported in part by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (Grant Nos. 20K16308 and 20K07594).

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Takeshi Morinaga MD, Masaaki Iwatsuki MD, PhD, Kohei Yamashita MD, PhD, Noriko Yasuda-Yoshihara PhD, Taishi Yamane MD, Chihiro Matsumoto MD, Kazuto Harada MD, PhD, Kojiro Eto MD, PhD, Junji Kurashige MD, PhD, Takatsugu Ishimoto MD, PhD, Yoshifumi Baba MD, PhD, Yuji Miyamoto MD, PhD, Naoya Yoshida MD, PhD & Hideo Baba MD, PhD

Authors
  1. Takeshi Morinaga MD
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  2. Masaaki Iwatsuki MD, PhD
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  3. Kohei Yamashita MD, PhD
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  4. Noriko Yasuda-Yoshihara PhD
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  5. Taishi Yamane MD
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  6. Chihiro Matsumoto MD
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  7. Kazuto Harada MD, PhD
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  8. Kojiro Eto MD, PhD
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  9. Junji Kurashige MD, PhD
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  10. Takatsugu Ishimoto MD, PhD
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  11. Yoshifumi Baba MD, PhD
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  12. Yuji Miyamoto MD, PhD
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  13. Naoya Yoshida MD, PhD
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  14. Hideo Baba MD, PhD
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Corresponding author

Correspondence to Hideo Baba MD, PhD.

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Disclosure

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 have no conflicts of interest to declare.

Ethics statement

Ethical approval for this study was granted by the Ethical Committee at Kumamoto University Hospital (Approval Number: 2365). Written informed consent was obtained from all participants included in this study, which was conducted in accordance with the Declaration of Helsinki principles.

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Morinaga, T., Iwatsuki, M., Yamashita, K. et al. Dynamic Alteration in HLA-E Expression and Soluble HLA-E via Interaction with Natural Killer Cells in Gastric Cancer. Ann Surg Oncol 30, 1240–1252 (2023). https://doi.org/10.1245/s10434-022-12505-0

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