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帕博利珠单抗对晚期非小细胞肺癌患者T淋巴细胞亚群的影响及其治疗效果

[Effect of Pembrolizumab on T Lymphocyte Subsets in Patients with Advanced 
Non-small Cell Lung Cancer and Its Therapeutic Effect].

作者信息

Wang Yun, Wang Yuyang, Jiang Man, Zhao Yuemei, Zhang Xiaochun

机构信息

Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.

Weifang People's Hospital of Shandong Province, Weifang 261000, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2021 Mar 20;24(3):182-187. doi: 10.3779/j.issn.1009-3419.2021.103.03.

Abstract

BACKGROUND

The aim of this study is to investigate the changes of peripheral blood lymphocyte subsets before and after treatment with pembrolizumab for non-small cell lung cancer and its clinical significance.

METHODS

A total of 32 patients with non-small cell lung cancer who received pembrolizumab treatment in The Affiliated Hospital of Qingdao University and Weifang People's Hospital of Shandong Province from January 2015 to December 2020 were selected as the observation group, and 30 healthy people during the same period were selected as the control group. Before treatment and in cycles 1, 2 and 4 after treatment, fluid cytometry was used to detect changes in the levels of lymphocyte subsets in the peripheral blood of patients.

RESULTS

The CD3⁺, CD4⁺, CD4⁺/CD8⁺ indexes of patients with non-small cell lung cancer before the treatment were significantly lower than those in the control group (P<0.05), and the CD8⁺ level was significantly increased (P<0.05); After 1 cycle of pembrolizumab treatment, there was no significant difference in the changes of lymphocyte subsets compared with before immunotherapy; After 2 cycles of the treatment, the CD3⁺, CD4⁺, CD4⁺/CD8⁺ values were higher than before the treatment (P>0.05), and the CD8⁺ index was slightly lower than before the treatment (P<0.05); After the fourth cycle of treatment, the CD3⁺, CD4⁺, CD4⁺/CD8⁺ values were significantly improved compared to before the treatment (P<0.05), and the CD8⁺ index was significantly lower than before the treatment (P<0.05); In the treatment process of patients with stable disease (SD)/partial response (PR), the CD3⁺, CD4⁺, CD4⁺/CD8⁺ values of the fourth cycles were higher than before the treatment (P<0.05), and the CD8⁺ index was lower than before the treatment (P<0.05); During the treatment of progressive disease (PD) patients, the changes of lymphocyte subsets in the fourth cycles were not significantly different from those before the treatment (P>0.05). At the same time, this article shows through analysis that the expression of programmed cell death ligand 1 (PD-L1) and pathological types have no obvious influence on the effect of immunotherapy. Multi-factor analysis shows that it is more meaningful to observe the changes of CD3⁺, CD4⁺ and CD8⁺ at the same time to predict the effect of immunotherapy.

CONCLUSIONS

Pembrolizumab can regulate the changes of T lymphocyte subsets in patients with non-small cell lung cancer, improve the immune status of the patients, and there is no obvious adverse reaction. At the same time, monitoring the changes of lymphocyte subsets during treatment can predict the effect of immunotherapy.

摘要

背景

本研究旨在探讨帕博利珠单抗治疗非小细胞肺癌前后外周血淋巴细胞亚群的变化及其临床意义。

方法

选取2015年1月至2020年12月在青岛大学附属医院和山东省潍坊市人民医院接受帕博利珠单抗治疗的32例非小细胞肺癌患者作为观察组,同期选取30例健康人作为对照组。在治疗前及治疗后第1、2、4周期,采用流式细胞术检测患者外周血淋巴细胞亚群水平的变化。

结果

非小细胞肺癌患者治疗前CD3⁺、CD4⁺、CD4⁺/CD8⁺指标显著低于对照组(P<0.05),CD8⁺水平显著升高(P<0.05);帕博利珠单抗治疗1周期后,淋巴细胞亚群变化与免疫治疗前相比无显著差异;治疗2周期后,CD3⁺、CD4⁺、CD4⁺/CD8⁺值高于治疗前(P>0.05),CD8⁺指标略低于治疗前(P<0.05);治疗第4周期后,CD3⁺、CD4⁺、CD4⁺/CD8⁺值较治疗前显著改善(P<0.05),CD8⁺指标显著低于治疗前(P<0.05);疾病稳定(SD)/部分缓解(PR)患者治疗过程中,第4周期CD3⁺、CD4⁺、CD4⁺/CD8⁺值高于治疗前(P<0.05),CD8⁺指标低于治疗前(P<0.05);疾病进展(PD)患者治疗期间,第4周期淋巴细胞亚群变化与治疗前无显著差异(P>0.05)。同时,本文通过分析表明,程序性细胞死亡配体1(PD-L1)的表达及病理类型对免疫治疗效果无明显影响。多因素分析表明,同时观察CD3⁺、CD4⁺和CD8⁺的变化对预测免疫治疗效果更有意义。

结论

帕博利珠单抗可调节非小细胞肺癌患者T淋巴细胞亚群变化,改善患者免疫状态,且无明显不良反应。同时,治疗期间监测淋巴细胞亚群变化可预测免疫治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e35/8143964/cc167dfbeabd/zgfazz-24-3-182-1.jpg

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