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化疗对晚期非小细胞肺癌患者血液淋巴细胞和生存的免疫调节作用。

Immunomodulatory effects of chemotherapy on blood lymphocytes and survival of patients with advanced non-small cell lung cancer.

机构信息

1 Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China.

2 Department of Respiratory, Nanjing Chest Hospital, Nanjing, People's Republic of China.

出版信息

Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419839592. doi: 10.1177/2058738419839592.

Abstract

A better understanding of the immune profile of non-small cell lung cancer (NSCLC) and the immunomodulatory impact of chemotherapy is essential to develop current therapeutic approaches. Herein, we collected peripheral blood from 20 healthy donors and 50 patients with advanced NSCLC, before and after chemotherapy, followed by phenotypic analysis of lymphocyte subsets and assessment of the correlation between their post-chemotherapy levels and progression-free survival (PFS). Results showed that, before chemotherapy, the levels of CD8 lymphocytes, PD-1CD4, Th2, and Th17 cells were elevated in patients' peripheral blood, in contrast to natural killer (NK) cells and Th1 cells. Besides, there was no remarkable difference in the frequency of PD-1CD8 cells between patients and healthy controls. After chemotherapy, the levels of CD8 lymphocytes, NK, Th2, Th17, and Treg were declined, in contrast to the level of Th1 cells which was markedly increased. Importantly, chemotherapy had no impact on the frequencies of PD-1CD8 and PD-1CD4 cells. PFS was significantly better in patients with low percentage of PD-1CD4 T cells than those with high percentage. Patients with high content of Th1 cells showed longer PFS than those with low content. The low percentages of Th17 and Treg cells were correlated with longer PFS, even though the difference did not reach statistical significance. In conclusion, the imbalance of lymphocyte subsets is a hallmark of NSCLC. Furthermore, the high level of PD-1CD4 cells plays a crucial role in the progression of NSCLC and could be used as a prognostic marker; and the high level of Th1 could predict better clinical outcomes of chemotherapy.

摘要

更好地了解非小细胞肺癌(NSCLC)的免疫特征和化疗的免疫调节作用,对于开发当前的治疗方法至关重要。在此,我们收集了 20 名健康供体和 50 名晚期 NSCLC 患者的外周血,分别在化疗前后进行淋巴细胞亚群的表型分析,并评估其化疗后水平与无进展生存期(PFS)之间的相关性。结果表明,化疗前,患者外周血中 CD8 淋巴细胞、PD-1CD4、Th2 和 Th17 细胞水平升高,而自然杀伤(NK)细胞和 Th1 细胞水平降低。此外,患者和健康对照组之间 PD-1CD8 细胞的频率没有显著差异。化疗后,CD8 淋巴细胞、NK、Th2、Th17 和 Treg 细胞水平下降,而 Th1 细胞水平显著升高。重要的是,化疗对 PD-1CD8 和 PD-1CD4 细胞的频率没有影响。与 PD-1CD4 T 细胞百分比高的患者相比,PD-1CD4 T 细胞百分比低的患者 PFS 明显更好。Th1 细胞含量高的患者 PFS 较长,而 Th1 细胞含量低的患者 PFS 较短。Th17 和 Treg 细胞的低百分比与较长的 PFS 相关,尽管差异没有达到统计学意义。总之,淋巴细胞亚群的失衡是非小细胞肺癌的一个标志。此外,PD-1CD4 细胞的高水平在 NSCLC 的进展中起着关键作用,可作为预后标志物;高水平的 Th1 可预测化疗的更好临床结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66fb/6458672/11d912ef75c3/10.1177_2058738419839592-fig1.jpg

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