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鼻咽癌放化疗患者循环免疫细胞的异常变化及预后意义:一项前瞻性队列研究

Abnormal variation and prognostic significance of circulating immune cells in patients with nasopharyngeal carcinoma treated with chemoradiotherapy: a prospective cohort study.

作者信息

Huang Chaoxiong, Ding Jianming, Huang Chuanzhong, Yu Ligen, Chitapanarux Imjai, Mejia Michael Benedict A, Fei Zhaodong, Chen Chuanben

机构信息

Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.

Office of Data and Analytics, Nanyang Technological University, Singapore, Singapore.

出版信息

Transl Cancer Res. 2023 Dec 31;12(12):3718-3727. doi: 10.21037/tcr-23-2024. Epub 2023 Dec 14.

DOI:10.21037/tcr-23-2024
PMID:38192995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10774047/
Abstract

BACKGROUND

Circulating immune cells are associated with tumor development and poor prognosis in multiple solid tumors. However, the circulating immune-cell profile of nasopharyngeal carcinoma (NPC) remains largely unknown. Therefore, we aimed to determine the changes in immune status and the prognostic significance of circulating immune cells before and after chemoradiotherapy (CRT) in patients, which can provide clinicians with valuable insights to optimize treatment strategies, monitor immune function, and personalize interventions, ultimately improving patient outcomes.

METHODS

Circulating immune cells before and after CRT in 77 patients with NPC and in 30 healthy controls were measured with flow cytometry. A thorough follow-up was conducted to assess prognosis outcomes, including local failure-free rate (LFFR), distant failure-free rate (DFFR), disease-free survival (DFS), and overall survival (OS). The differences of the subpopulation distribution in the two groups were determined by -tests or Mann-Whitney tests. The paired -test or Wilcoxon matched-pairs signed rank test was used to compare differences in lymphocyte subsets before and after CRT. The prognostic significance of lymphocyte subsets was evaluated by Kaplan-Meier analysis and Cox proportional hazards model.

RESULTS

Compared with the control group, the NPC group showed significant decreases in the proportions of CD3 cells, CD4 T cells, CD8CD28 T cells, and CD19 B cells as well as the CD4:CD8 ratio (P<0.05) but a significant increase in the proportion of natural killer (NK) cells (P<0.05). After CRT, the proportions of CD4 cells, CD8CD28 T cells, and CD19 B cells as well as the CD4:CD8 ratio were markedly decreased (P<0.05), while the proportions of CD8 T cells and NK cells were significantly increased (P<0.05). Multivariate analysis showed that a lower percentage of CD19 B cells [hazard ratio (HR) 6.550, 95% CI: 1.661-25.831; P=0.007] and a positive test for Epstein-Barr virus (EBV) DNA (HR 0.261, 95% CI: 0.074-0.926; P=0.038) before treatment independently predicted worse 5-year OS (P<0.05).

CONCLUSIONS

The disproportion of circulating immune cells was observed in patients with NPC before treatment. CRT further aggravated immune dysfunction. Notably, a lower percentage of CD19 B cells and EBV DNA-positive status before treatment were independent predictors of a worse prognosis. Thus, the measurement of circulating immune cells may help elucidate immune function status and predict the outcomes of patients with NPC.

摘要

背景

循环免疫细胞与多种实体瘤的肿瘤发生及不良预后相关。然而,鼻咽癌(NPC)的循环免疫细胞谱在很大程度上仍不清楚。因此,我们旨在确定患者放化疗(CRT)前后免疫状态的变化以及循环免疫细胞的预后意义,这可为临床医生优化治疗策略、监测免疫功能及实施个性化干预提供有价值的见解,最终改善患者预后。

方法

采用流式细胞术检测77例NPC患者及30例健康对照者CRT前后的循环免疫细胞。进行全面随访以评估预后结果,包括局部无失败率(LFFR)、远处无失败率(DFFR)、无病生存期(DFS)和总生存期(OS)。两组亚群分布的差异通过t检验或Mann-Whitney检验确定。采用配对t检验或Wilcoxon配对符号秩检验比较CRT前后淋巴细胞亚群的差异。通过Kaplan-Meier分析和Cox比例风险模型评估淋巴细胞亚群的预后意义。

结果

与对照组相比,NPC组CD3细胞、CD4 T细胞、CD8CD28 T细胞和CD19 B细胞的比例以及CD4:CD8比值显著降低(P<0.05),但自然杀伤(NK)细胞比例显著升高(P<0.05)。CRT后,CD4细胞、CD8CD28 T细胞和CD19 B细胞的比例以及CD4:CD8比值明显降低(P<0.05),而CD8 T细胞和NK细胞的比例显著升高(P<0.05)。多因素分析显示,治疗前CD19 B细胞百分比降低[风险比(HR)6.550,95%可信区间(CI):1.661-25.831;P=0.007]和EB病毒(EBV)DNA检测阳性(HR 0.261,95%CI:0.074-0.926;P=0.038)独立预测5年总生存期较差(P<0.05)。

结论

治疗前NPC患者存在循环免疫细胞失衡。CRT进一步加重免疫功能障碍。值得注意的是,治疗前CD19 B细胞百分比降低和EBV DNA阳性状态是预后较差的独立预测因素。因此,检测循环免疫细胞可能有助于阐明NPC患者的免疫功能状态并预测其预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6bd/10774047/5cf079526ac4/tcr-12-12-3718-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6bd/10774047/518789644c80/tcr-12-12-3718-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6bd/10774047/5cf079526ac4/tcr-12-12-3718-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6bd/10774047/518789644c80/tcr-12-12-3718-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6bd/10774047/5cf079526ac4/tcr-12-12-3718-f2.jpg

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