RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
血红素加氧酶-1 通过下调人类白细胞抗原-C 抑制 NK 细胞对急性髓系白血病的细胞毒性
英文原题：Heme oxygenase-1 inhibits the cytotoxicity of natural killer cells to acute myeloid leukemia by downregulating human leukocyte antigen-C.
查看英文原题
Heme oxygenase-1 inhibits the cytotoxicity of natural killer cells to acute myeloid leukemia by downregulating human leukocyte antigen-C.
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研究概要
NK 细胞介导的固有免疫对于对抗肿瘤十分重要，尤其是在获得性免疫耗竭和功能障碍时，且 HO-1/HLA-C 轴可诱导 AML 中 NK 细胞的功能改变。
中文摘要
背景与目的
近年来，免疫逃逸被认为是急性髓系白血病（AML）复发的原因之一。我们既往研究证实，血红素加氧酶1（HO-1）在AML细胞增殖和耐药中发挥重要作用。此外，本组近期研究表明，HO-1参与AML免疫逃逸。但HO-1介导AML免疫逃逸的具体机制尚不清楚。
方法
本研究发现，HO-1过表达的AML患者复发率较高。体外实验中，HO-1过表达减弱了自然杀伤（NK）细胞对AML细胞的毒性作用。进一步研究表明，HO-1过表达可抑制人白细胞抗原C（HLA-C），降低NK细胞对AML细胞的细胞毒作用，从而导致AML复发。从机制上看，HO-1通过激活JNK/C-Jun信号通路抑制HLA-C表达。
结果
在AML中，HO-1通过抑制HLA-C表达降低NK细胞的细胞毒作用，进而导致AML细胞免疫逃逸。
结论
NK细胞介导的先天免疫对于抗击肿瘤非常重要，尤其是在获得性免疫耗竭和功能障碍时；HO-1/HLA-C轴可诱导AML患者NK细胞发生功能改变。抗HO-1治疗可增强NK细胞抗肿瘤作用，可能在AML治疗中发挥重要作用。
展开英文摘要原文
METHODS
In this study, we found that patients with AML and an overexpression of HO-1 had a high rate of recurrence. In vitro, overexpression of HO-1 attenuated the toxicity of natural killer (NK) cells to AML cells. Further study indicated that HO-1 overexpression inhibited human leukocyte antigen-C and reduced the cytotoxicity of NK cells to AML cells, leading to AML relapse. Mechanistically, HO-1 inhibited human leukocyte antigen-C expression by activating the JNK/C-Jun signaling pathway.
RESULTS
In AML, HO-1 inhibits cytotoxicity of NK cells by inhibiting the expression of HLA-C, thus causing immune escape of AML cells.
CONCLUSIONS
NK cell-mediated innate immunity is important for the fight against tumors, especially when acquired immunity is depleted and dysfunctional, and the HO-1/HLA-C axis can induce functional changes in NK cells in AML. Anti-HO-1 treatment can promote the antitumor effect of NK cells and may play an important role in the treatment of AML.
论文信息
- 作者
- Feng C、Zhang T、Pan C、Kang Q、Wang L、Liu X、Shang Q、Chen S
- 第一作者单位
- Clinical Medicine College of Guizhou Medical University, Guiyang, China; Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou Province Institute of Hematology, Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, Guiyang, China.China
- 通讯作者单位
- Clinical Medicine College of Guizhou Medical University, Guiyang, China; Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou Province Institute of Hematology, Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, Guiyang, China. Electronic address: wangjishi9646@163.com.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cytotherapy2023 Jul
- 原文标识
- PubMed 36890092 · DOI 10.1016/j.jcyt.2023.02.001