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肾癌患者淋巴细胞亚群和髓系抑制细胞临床意义的评估

Evaluation of the clinical significance of lymphocyte subsets and myeloid suppressor cells in patients with renal carcinoma.

作者信息

Li Yan, Wu Zhiping, Ni Chen, Li Yueda, Wang Ping

机构信息

Department of Nephrology, Third People's Hospital of Hangzhou, Hangzhou, 310009, Zhejiang, China.

出版信息

Discov Oncol. 2024 Sep 30;15(1):512. doi: 10.1007/s12672-024-01405-2.

Abstract

PURPOSE

The purpose of this study was to analyze the expression patterns of immune cells in renal cancer patients, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), CD3 + /CD4 + T cells, CD3 + / CD8 + T cells, and CD3- CD16 + CD56 + cells. In addition, this study will explore the correlation between these immune markers and the progression of renal cell carcinoma and evaluate their potential application in predicting the therapeutic effect of renal cell carcinoma.

METHODS

In this study, 80 renal cancer patients who received treatment in our hospital from October 2022 to December 2023 were selected as the research object and 50 healthy people who underwent a physical examination at the same time were selected as the control group. All participants had a 3 ml venous blood sample taken in the morning on an empty stomach. All patients with renal cell carcinoma have been confirmed by histopathological diagnosis. Clinicopathological data including age, gender, BMI, clinical stage, tumor size and pathological type were collected.MDSC, Treg, CD3 + /CD4 + T cells, CD3 + /CD8 + T cells, the ratio of CD3 + /CD4 + T cells/CD3 + /CD8 + T cell and the expression level of CD3-CD16 + CD56 + cells were detected by flow cytometry.

RESULTS

Through the detection of flow cytometry, we observed that there was no significant difference in gender, age, BMI and other baseline characteristics between renal cancer patients and healthy controls, and the P value was greater than 0.05. However, in the analysis of peripheral blood immune cell subsets, including CD3 + /CD4 + , CD3 + /CD8 + , CD3 + /CD4 + /CD3 + /CD8 + ratio, NK cells, regulatory T cells (T-reg), polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and mononuclear myeloid-derived suppressor cells (M-MDSC) were significantly different between renal cell carcinoma group and normal control group (P < 0.05). Specifically, the expression levels of CD3 + /CD4 + and CD3 + /CD8 + cells in renal cancer patients were lower than those in normal subjects, while the expression levels of T-reg, PMN-MDSC and M-MDSC were relatively high. (2) In the flow cytometry analysis, the expression level of immune cell subsets in the peripheral blood of renal cancer patients was detected.The results showed that there was no significant correlation between the expression of CD3 + /CD4 + , CD3 + /CD8 + , CD3 + /CD4 + /CD3 + /CD8 + ratio, NK cells, T-reg cells, PMN-MDSC and M-MDSC and the sex, age, BMI and pathological type of the patients. These differences were not statistically significant (P > 0.05).At the same time, CD3 + /CD8 + T cells, the ratio of CD3 + /CD4 + /CD3 + /CD8 + and the expression level of NK cells were not significantly correlated with tumor size and clinical stage (P > 0.05). However, the expression levels of CD3 + /CD4 + cells, M-MDSC, PMN-MDSC, and T-reg cells were statistically significantly different with tumor size and clinical stage (P < 0.05).There was a significant difference between these indexes and lymph node metastasis (P < 0.05). (3) The results of Logistic regression analysis showed that the low expression of CD3 + /CD4 + lymphocytes and the high expression of T-reg, PMN-MDSC and M-MDSC in peripheral blood may be related to the clinical stage of renal cell carcinoma.

CONCLUSION

(1) Compared with healthy individuals, patients with renal cell carcinoma showed a significant decrease in CD3 + /CD4 + T cells, CD3 + /CD8 + T cells and CD3-CD16 + CD56 + cells, while the CD4 + /CD8 + ratio increased. In addition, the number of PMN-MDSC, M-MDSC and T-reg cells was significantly increased compared with the normal population, indicating that the immune system function of patients was impaired. (2) The expression levels of CD3 + /CD4 + , PMN-MDSC, M-MDSC and T-reg were different in tumor size and clinical stage. Specifically, the expression levels of PMN-MDSC, M-MDSC, and T-reg increased correspondingly with the increase in tumor diameter and the progression of the clinical stage.

摘要

目的

本研究旨在分析肾癌患者中免疫细胞的表达模式,包括髓源性抑制细胞(MDSCs)、调节性T细胞(Tregs)、CD3 + /CD4 + T细胞、CD3 + /CD8 + T细胞和CD3 - CD16 + CD56 +细胞。此外,本研究将探讨这些免疫标志物与肾细胞癌进展之间的相关性,并评估它们在预测肾细胞癌治疗效果方面的潜在应用。

方法

本研究选取2022年10月至2023年12月在我院接受治疗的80例肾癌患者作为研究对象,同时选取50例同期进行体检的健康人作为对照组。所有参与者均于清晨空腹采集3ml静脉血样。所有肾细胞癌患者均经组织病理学诊断确诊。收集包括年龄、性别、BMI、临床分期、肿瘤大小和病理类型在内的临床病理数据。通过流式细胞术检测MDSC、Treg、CD3 + /CD4 + T细胞、CD3 + /CD8 + T细胞、CD3 + /CD4 + T细胞/CD3 + /CD8 + T细胞比值以及CD3 - CD16 + CD56 +细胞的表达水平。

结果

通过流式细胞术检测,我们观察到肾癌患者与健康对照在性别、年龄、BMI等基线特征方面无显著差异,P值大于0.05。然而,在对外周血免疫细胞亚群的分析中,包括CD3 + /CD4 +、CD3 + /CD8 +、CD3 + /CD4 + /CD3 + /CD8 +比值、自然杀伤细胞(NK细胞)、调节性T细胞(T-reg)、多形核髓源性抑制细胞(PMN-MDSC)和单核髓源性抑制细胞(M-MDSC),肾细胞癌组与正常对照组之间存在显著差异(P < 0.05)。具体而言,肾癌患者中CD3 + /CD4 +和CD3 + /CD8 +细胞的表达水平低于正常受试者,而T-reg、PMN-MDSC和M-MDSC的表达水平相对较高。(2)在流式细胞术分析中,检测了肾癌患者外周血中免疫细胞亚群的表达水平。结果显示,CD3 + /CD4 +、CD3 + /CD8 +、CD3 + /CD4 + /CD3 + /CD8 +比值、NK细胞、T-reg细胞、PMN-MDSC和M-MDSC的表达与患者的性别、年龄、BMI和病理类型之间无显著相关性。这些差异无统计学意义(P > 0.05)。同时,CD3 + /CD8 + T细胞、CD3 + /CD4 + /CD3 + /CD8 +比值以及NK细胞的表达水平与肿瘤大小和临床分期无显著相关性(P > 0.05)。然而,CD3 + /CD4 +细胞、M-MDSC、PMN-MDSC和T-reg细胞的表达水平与肿瘤大小和临床分期在统计学上有显著差异(P < 0.05)。这些指标与淋巴结转移之间存在显著差异(P < 0.05)。(3)Logistic回归分析结果显示,外周血中CD3 + /CD4 +淋巴细胞低表达以及T-reg、PMN-MDSC和M-MDSC高表达可能与肾细胞癌的临床分期有关。

结论

(1)与健康个体相比,肾细胞癌患者的CD3 + /CD4 + T细胞、CD3 + /CD8 + T细胞和CD3 - CD16 + CD56 +细胞显著减少,而CD4 + /CD8 +比值升高。此外,与正常人群相比,PMN-MDSC、M-MDSC和T-reg细胞数量显著增加,表明患者的免疫系统功能受损。(2)CD3 + /CD4 +、PMN-MDSC、M-MDSC和T-reg的表达水平在肿瘤大小和临床分期方面存在差异。具体而言,PMN-MDSC、M-MDSC和T-reg的表达水平随着肿瘤直径的增加和临床分期的进展而相应升高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a7/11442913/698f5a3fd230/12672_2024_1405_Fig1_HTML.jpg

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