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
脐血移植中移植物抗宿主病预防改变杀伤细胞免疫球蛋白样受体-配体错配效应
英文原题：Altered effect of killer immunoglobulin-like receptor-ligand mismatch by graft versus host disease prophylaxis in cord blood transplantation.
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Altered effect of killer immunoglobulin-like receptor-ligand mismatch by graft versus host disease prophylaxis in cord blood transplantation.
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中文摘要
供者与受者之间杀伤细胞免疫球蛋白样受体-配体错配（KIR-配体错配）在接受脐血移植（CBT）中的作用存在争议。如果每种免疫抑制剂对自然杀伤（NK）细胞功能的影响不同，那么KIR-配体错配的效应可能因移植物抗宿主病（GVHD）预防方案的类型而改变。为验证这一假设，本研究回顾性评估了因急性白血病、骨髓增生异常综合征或慢性髓性白血病接受CBT的患者之间，以及包含他克莫司联合甲氨蝶呤（MTX）或霉酚酸酯（MMF）的GVHD预防方案之间，KIR-配体错配效应的差异。在MMF组（n = 1363）中，KIR-配体错配增加了非复发死亡率（NRM；风险比[HR]，1.40；P = 0.008），并使总生存期（OS）恶化（HR，1.30，P = 0.0077）。在对每种KIR-配体错配类型的分析中，HLA-C2错配仅在MTX组中对复发发生率（HR，0.56；P = 0.0043）和OS（HR，0.72；P = 0.037）具有有利影响。在MMF组中，HLA-A3/A11错配使NRM（HR，1.93；P < 0.001）和OS（HR，1.48；P = 0.014）恶化。这些结果提示，KIR-配体错配的效应因GVHD预防方案的类型而异，并且评估KIR-配体错配状态对CBT具有重要意义。
展开英文摘要原文
The role of killer immunoglobulin-like receptor-ligand mismatch (KIR-ligand mismatch) between donors and recipients undergoing cord blood transplantation (CBT) is controversial. If each immunosuppressant differently affects natural killer (NK) cell function, the effect of KIR-ligand mismatch may be altered depending on the type of graft versus host disease (GVHD) prophylaxis. To verify this hypothesis, the difference in the effect of KIR-ligand mismatch was retrospectively assessed between patients who received CBT for acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia, as well as GVHD prophylaxis comprising tacrolimus plus methotrexate (MTX) or mycophenolate mofetil (MMF).
In the MMF group (n = 1363), KIR-ligand mismatch augmented the incidence of non-relapse mortality (NRM; hazard ratio [HR], 1. 40; P = 0. 008), which worsened overall survival (OS; HR, 1. 30, P = 0. 0077). In the analysis of each KIR-ligand mismatch type, HLA-C2 mismatch had a favorable effect on relapse incidence (HR, 0. 56; P = 0.
0043) and OS (HR, 0. 72; P = 0. 037) only in the MTX group. In the MMF group, HLA-A3/A11 mismatch worsened NRM (HR, 1. 93; P < 0. 001) and OS (HR, 1. 48; P = 0. 014). These results imply that the effects of KIR-ligand mismatch differ with the type of GVHD prophylaxis and that assessing the KIR-ligand mismatch status is important for CBT.
论文信息
- 作者
- Yokoyama H、Hirayama M、Takahashi Y、Uchida N、Tanaka M、Onizuka M、Ozawa Y、Onai D
- 单位
- Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan. hisayuki.yokoyama.a1@tohoku.ac.jp.Japan
- 期刊
- Bone marrow transplantation2021 Dec
- 原文标识
- PubMed 34561558 · DOI 10.1038/s41409-021-01469-6