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
使用活化 NK 细胞的免疫治疗改善肝细胞癌活体肝移植受者的术后中性粒细胞与淋巴细胞比值及长期预后
英文原题：Immunotherapy Using Activated Natural Killer Cells Improves Postoperative Neutrophil-to-Lymphocyte Ratio and Long-Term Prognosis of Living Donor Liver Transplant Recipients With Hepatocellular Carcinoma.
查看英文原题
Immunotherapy Using Activated Natural Killer Cells Improves Postoperative Neutrophil-to-Lymphocyte Ratio and Long-Term Prognosis of Living Donor Liver Transplant Recipients With Hepatocellular Carcinoma.
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研究概要
术后 NLR 水平较高与 HCC 患者 LDLT 术后不良预后独立相关。使用活化 NK 细胞的免疫治疗可能改善术后 NLR 和长期预后。
研究思路结论见上方概要
目的
术前中性粒细胞与淋巴细胞比值（NLR）是多种恶性肿瘤中众所周知的预后指标；然而，术后NLR对活体肝移植（LDLT）受者的影响尚不清楚。供肝来源的活化自然杀伤（NK）细胞免疫治疗可能通过共激活免疫细胞或抑制活化的中性粒细胞来改善术后NLR。本研究旨在阐明术后NLR在合并HCC的LDLT受者中的临床意义，并评估免疫治疗是否改善术后NLR。
方法
我们开展了一项回顾性研究，纳入2001年至2022年间的LDLT受者，以评估术后NLR的临床意义。此外，还评估了术后NLR与输注NK细胞活化标志物之间的相关性。术后NLR于LDLT后4周进行检测。
结果
术后高 NLR 组（N = 78）较术后低 NLR 组（N = 41）术前 NLR 更低、终末期肝病模型评分更高，且 LDLT 术后 30 天内术后感染发生率更高。多因素分析显示，术后高 NLR（风险比 [HR]，2.62；95% 置信区间 [CI]，1.01-6.79；P = .047）和未接受免疫治疗（HR，3.10；95% CI，1.33-7.22；P < .01）是总生存期不良的独立危险因素。此外，输注 NK 细胞的活化标志物与术后 NLR 降低呈负相关。
展开英文摘要原文
OBJECTIVE
Preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic indicator in various malignancies; however, the impact of postoperative NLR on living donor liver transplant (LDLT) recipients is unknown. Immunotherapy with donor liver-derived activated natural killer (NK) cells may improve postoperative NLR by coactivating immune cells or suppressing activated neutrophils. This study aims to clarify the clinical significance of postoperative NLR in recipients after LDLT with HCC and assess whether immunotherapy improves postoperative NLR.
METHODS
We conducted a retrospective study of LDLT recipients between 2001 and 2022 to evaluate the clinical significance of postoperative NLR. Furthermore, the correlation between postoperative NLR and the activation marker of infused NK cells was also evaluated. The postoperative NLR was examined 4 weeks after LDLT.
RESULTS
The postoperative high NLR group (N = 78) had preoperative lower NLR and higher model for end-stage liver disease and a higher rate of postoperative infection within 30 days after LDLT than the postoperative low NLR group (N = 41). Postoperative high NLR (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.01-6.79; P = .047) and nontreatment of immunotherapy (HR, 3.10; 95% CI, 1.33-7.22; P < .01) were independent risk factors for poor overall survival in multivariate analysis. Furthermore, the activation marker of infused NK cells is inversely correlated with decreased postoperative NLR.
CONCLUSIONS
The higher level of postoperative NLR was independently associated with poor prognosis in patients after LDLT with HCC. Immunotherapy using activated NK cells may improve postoperative NLR and long-term prognosis.
论文信息
- 作者
- Imaoka K、Ohira M、Hattori M、Chogahara I、Sato S、Nakamura M、Bekki T、Sato K
- 第一作者单位
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.Japan
- 通讯作者单位
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan. Electronic address: mohira@hiroshima-u.ac.jp.Japan
- 期刊
- Transplantation proceedings2024 Apr
- 原文标识
- PubMed 38443302 · DOI 10.1016/j.transproceed.2024.02.002