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成熟 NK 细胞肿瘤免疫表型的鉴别诊断、治疗和预后价值的综合分析与总结。

Comprehensive Analysis and Summary of the Value of Immunophenotypes of Mature NK Cell Tumors for Differential Diagnosis, Treatment, and Prognosis.

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Key Clinical Laboratory of Henan Province, Zhengzhou University, Zhengzhou, China.

出版信息

Front Immunol. 2022 Jun 24;13:918487. doi: 10.3389/fimmu.2022.918487. eCollection 2022.

Abstract

BACKGROUND

Few studies have been performed to comprehensively analyze and summarize the immunophenotype and differential diagnosis of mature NK cell tumors, and there is often overlap between tumorigenic and reactive NK cell phenotypes. Furthermore, the impact of different phenotypes on patient prognosis has rarely been reported.

METHODS

The degree of expression of extracellular and intracellular markers of NK cells in each group was compared by FCM, and the differences in expression of various markers among different disease groups and their impact on prognosis have been analyzed and summarized.

RESULTS

Compared with normal NK cells, tumor cells of ANKL and ENKTL had characteristics of being more activated and progressive with larger FSC, in contrast to NK-CLPD and RNKL. Differential diagnoses with RNKL, ANKL, and ENKTL have broader FCM clues. In contrast, the phenotypes of NK-CLPD and RNKL are not significantly different, and consistent phenotypic abnormalities require ongoing monitoring to confirm malignant clones. The sensitivity of differentiating malignant NK cells from reactive NK cells by KIRs alone was poor. The clustering results showed that CD5, CD16, CD56, CD57, CD94, CD45RA, CD45RO, HLA-DR, KIRs, Granzyme B, Perforin and Ki-67 were differentially distributed in the expression of three NK cell tumors and reactive NK cell hyperplasia, so a comprehensive judgment using a wide range of antibody combinations is required in disease staging diagnosis. The tumor cell loads in BM and PB were also compared, and there was a clear correlation between the two. Moreover, the sensitivity of PB for monitoring tumor cells was up to 87.10%, suggesting that PB could be used as an alternative to BM for the diagnosis and screening of NK cell tumors. Analysis of the phenotypic impact of ENKTL patients on prognosis showed that those with CD7 and CD45RO expression had a poor prognosis, while those with positive KIRs had a better prognosis.

CONCLUSION

This study systematically characterized the FCM of mature NK cell tumors, emphasizing the importance and clinical value of accurate immunophenotyping in diagnosing, classifying, determining prognosis, and guiding treatment of the disease.

摘要

背景

目前鲜有研究能全面分析和总结成熟 NK 细胞肿瘤的免疫表型和鉴别诊断,而且肿瘤性和反应性 NK 细胞表型之间经常存在重叠。此外,不同表型对患者预后的影响也很少有报道。

方法

通过 FCM 比较各组 NK 细胞的细胞外和细胞内标志物的表达程度,并分析和总结不同疾病组之间各种标志物的表达差异及其对预后的影响。

结果

与正常 NK 细胞相比,ANKL 和 ENKTL 肿瘤细胞具有更大的 FSC,表现为更活跃和更具侵袭性,而 NK-CLPD 和 RNKL 则相反。与 RNKL、ANKL 和 ENKTL 的鉴别诊断有更广泛的 FCM 线索。相比之下,NK-CLPD 和 RNKL 的表型没有明显差异,持续的监测以确认恶性克隆是必要的。仅通过 KIR 区分恶性 NK 细胞与反应性 NK 细胞的敏感性较差。聚类结果表明,CD5、CD16、CD56、CD57、CD94、CD45RA、CD45RO、HLA-DR、KIRs、Granzyme B、Perforin 和 Ki-67 在三种 NK 细胞肿瘤和反应性 NK 细胞增生中的表达存在差异分布,因此需要使用广泛的抗体组合进行综合判断,以进行疾病分期诊断。还比较了 BM 和 PB 中的肿瘤细胞负荷,两者之间存在明显的相关性。此外,PB 监测肿瘤细胞的敏感性高达 87.10%,表明 PB 可替代 BM 用于 NK 细胞肿瘤的诊断和筛查。对 ENKTL 患者的表型对预后的影响进行分析表明,表达 CD7 和 CD45RO 的患者预后较差,而表达 KIRs 的患者预后较好。

结论

本研究系统地描述了成熟 NK 细胞肿瘤的 FCM,强调了准确免疫表型在诊断、分类、确定预后和指导疾病治疗方面的重要性和临床价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fb8/9263723/313b52ea611a/fimmu-13-918487-g001.jpg

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