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免疫疗法联合活化自然杀伤细胞可改善肝癌活体肝移植受者术后中性粒细胞与淋巴细胞比值和长期预后

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.

机构信息

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

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.

出版信息

Transplant Proc. 2024 Apr;56(3):634-639. doi: 10.1016/j.transproceed.2024.02.002. Epub 2024 Mar 4.

DOI:10.1016/j.transproceed.2024.02.002
PMID:38443302
Abstract

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.

摘要

目的

术前中性粒细胞与淋巴细胞比值(NLR)是多种恶性肿瘤中一种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。供肝来源的激活自然杀伤(NK)细胞免疫疗法通过共激活免疫细胞或抑制激活的中性粒细胞,可能改善术后 NLR。本研究旨在阐明 HCC 患者 LDLT 后受者术后 NLR 的临床意义,并评估免疫疗法是否改善术后 NLR。

方法

我们对 2001 年至 2022 年间接受 LDLT 的患者进行了回顾性研究,以评估术后 NLR 的临床意义。此外,还评估了术后 NLR 与输注 NK 细胞激活标志物之间的相关性。术后 NLR 在 LDLT 后 4 周进行检查。

结果

术后高 NLR 组(N = 78)术前 NLR 较低,终末期肝病模型(MELD)评分较高,术后 30 天内感染率高于术后低 NLR 组(N = 41)。多因素分析显示,术后高 NLR(危险比 [HR],2.62;95%置信区间 [CI],1.01-6.79;P =.047)和未行免疫治疗(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 细胞的激活标志物与术后 NLR 的降低呈负相关。

结论

术后 NLR 水平较高与 HCC 患者 LDLT 后预后不良独立相关。使用激活 NK 细胞的免疫疗法可能改善术后 NLR 和长期预后。

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