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
认识视网膜母细胞瘤中的杀伤细胞免疫球蛋白样受体多态性
英文原题：Understanding the killer-cell immunoglobulin like receptor polymorphism in retinoblastoma.
查看英文原题
Understanding the killer-cell immunoglobulin like receptor polymorphism in retinoblastoma.
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研究概要
这是首次报道杀伤细胞免疫球蛋白样受体与视网膜母细胞瘤关联的研究。KIR2DS4*FUL 和 KIR2DS5 对视网膜母细胞瘤具有易感作用，而 KIR3DS1/HLA-BW4 具有保护作用。该结果将有助于探索基于 NK 细胞疗法对视网膜母细胞瘤的治疗潜力。
研究思路结论见上方概要
背景
自然杀伤（NK）细胞上的KIR受体通过发挥细胞毒性消除肿瘤细胞，起着至关重要的作用。KIR和I类HLA分子均表现出广泛的多态性。尽管RB1失活触发视网膜母细胞瘤的发生；然而额外的免疫改变触发肿瘤发展。目的是探讨KIR/HLA多态性及其在视网膜母细胞瘤发病机制中的作用。
方法
单侧、非家族性视网膜母细胞瘤患者作为病例入组。按种族匹配的健康个体作为对照入组。采用序列特异性引物测定法进行KIR基因分型。所研究的KIR基因包括：抑制性（2DL1、2DL2、2DL3、2DL4、2DL5A、2DL5B）、激活性（2DS1、2DS2、2DS3、2DS4*FUL、2DS4*DEL、2DS5、3DL1、3DL2、3DL3、3DS1）和假基因（2DP1、3DP1*FUL、3DP1*DEL）。此外，通过序列特异性寡核苷酸测定法检测HLA-A、B和C位点的HLA配体。
结果
对48例病例和107例对照进行了KIR基因分型。病例的平均年龄为2.9±2.2岁（范围：0.25-10）。在19个KIR基因中，KIR2DS4*FUL（p = 0.0019）和2DS5（p = 0.0095）的频率在病例中升高。对25例病例和50例对照进行了HLA配体研究。HLA配体（C1/C2、Bw4、A3/A11）的频率在病例和对照之间相似。然而，KIR3DS1/HLA-Bw4的KIR/HLA组合频率在病例中降低（p = 0.006）。
展开英文摘要原文
BACKGROUND
The KIR receptors present on the natural killer (NK) cells play a crucial role by exercising cytotoxicity to eliminate tumor cells. Both KIR and class-I HLA molecules exhibit extensive polymorphism. Although RB1 inactivation triggers the initiation of retinoblastoma; however additional immune alterations trigger tumor development. The aim was to explore the KIR/HLA polymorphism and its role in the pathogenesis of retinoblastoma.
METHODS
Patients with unilateral, non-familial retinoblastoma were enrolled as cases. Healthy individuals matched for ethnicity were enrolled as controls. KIR genotyping was performed by sequence-specific primer assay. The investigated KIR genes included: inhibitory (2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B), activating (2DS1, 2DS2, 2DS3, 2DS4*FUL, 2DS4*DEL, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and pseudogenes (2DP1, 3DP1*FUL, 3DP1*DEL). In addition, HLA ligands were investigated by sequence-specific oligonucleotide assay for HLA-A, B, and C locus.
RESULTS
KIR genotyping was performed in 48 cases and 107 controls. The mean age of cases was 2.9 2.2 years (range: 0.25-10). Among the 19 KIR genes, the frequency of KIR2DS4*FUL ( p = 0.0019) and 2DS5 ( p = 0.0095) was increased among cases. HLA ligands were investigated in 25 cases and 50 controls. The frequency of HLA ligands (C1/C2, Bw4, A3/A11) was similar among cases and controls. However, the KIR/HLA combination frequency for KIR3DS1/HLA-Bw4 was decreased in cases ( p = 0.006).
CONCLUSION
It is the pioneer study to report the association of killer cell immunoglobulin-like receptors in retinoblastoma. KIR2DS4*FUL and KIR2DS5 had a susceptible, and KIR3DS1/HLA-BW4 had a protective role in retinoblastoma. The results will aid in exploring the therapeutic potential of NK cell-based therapy for retinoblastoma.
论文信息
- 作者
- Aggarwal R、Sharma M、Singh U、Poulton K、Bhatia T、Mangat N、Kakkar N、Bansal D
- 第一作者单位
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.India
- 通讯作者单位
- Hematology-Oncology unit, Department of Pediatrics, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India.India
- 文献类型
- 非美国政府资助研究
- 期刊
- Ophthalmic genetics2023 Feb
- 原文标识
- PubMed 36594723 · DOI 10.1080/13816810.2022.2163404