Dynamic Alteration in HLA-E Expression and Soluble HLA-E via Interaction with Natural Killer Cells in Gastric Cancer
Dynamic Alteration in HLA-E Expression and Soluble HLA-E via Interaction with Natural Killer Cells in Gastric Cancer
复制标题
DOI：
10.1245/s10434-022-12505-0
复制
发表时间：
2022-09-23
影响因子：
3.7
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
--
作者：
Morinaga, Takeshi;Iwatsuki, Masaaki;Baba, Hideo
一些报道显示可溶性人白细胞抗原E （HLA-E）的免疫耐受，但可溶性HLA-E在胃癌（GC）中的作用尚不清楚。我们旨在阐明GC中可溶性HLA-E的分子机制及临床意义。方法观察GC细胞和可溶性HLA-E在自然杀伤细胞（NK）共培养下的表达情况。在可溶性HLA-E存在的情况下，使用抗NK 2组成员A （NKG2A）抗体研究NK细胞活性的变化。测定GC患者血清中可溶性HLA-E的表达。结果NK细胞分泌干扰素(IFN)- γ时，GC细胞的HLA-E表达呈时间依赖性，可溶性HLA-E在条件培养基中表达上调。在可溶性HLA-E存在的情况下，抗NKG2A抗体的预孵育增加了NKG2A(+) NK细胞的活化。GC患者血清中可溶性HLA-E的表达与疾病进展相关。结论HLA-E在GC细胞和条件培养基中的表达是动态变化的。此外，可溶性HLA-E可以促进GC细胞系的免疫逃逸，这可能在临床应用中具有重要意义。此外，可溶性HLA-E可能是一种潜在的预后生物标志物。
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)-gamma 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.