摘要: |
目的:探讨一线和二线免疫治疗对非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床疗效及外周血免疫抑制细胞的影响。方法:选择2018年1月至2019年10月复旦大学附属中山医院收治的NSCLC患者27例,其中接受PD-1抑制剂一线免疫治疗者7例(一线组)、二线免疫治疗20例(二线组),分析PD-1抑制剂一线和二线免疫治疗对27例NSCLC患者的临床疗效及对外周血主要免疫抑制细胞,包括单核细胞-髓系来源抑制性细胞(monocytic myeloid-derived suppressor cells,M-MDSCs)、粒细胞-髓系来源抑制性细胞(granulocytic myeloid-derived suppressor cells,G-MDSCs)和调节性T细胞(regulatory T cells,Tregs)的影响。结果:一线组中,57.1%(4/7)患者部分缓解(partial response,PR),28.6%(2/7)疾病稳定(stable disease,SD),14.3%(1/7)疾病进展(progressive disease,PD)。二线组中,15%(3/20)为PR,55%(11/20)为SD,30%(6/20)为PD。流式细胞仪分析发现,在第1次免疫治疗(3周)后,一线组M-MDSCs显著下降(P<0.05),而二线组治疗前后差异无统计学意义;一线组较二线组M-MDSCs水平更低,但G-MDSCs没有相应变化;Tregs水平在2组中均显著上升,但二线组上升趋势更加明显。相关性分析显示,M-MDSCs下降值与疗效相关(r=-0.04,P<0.05),Tregs增加值与疗效不相关。结论:晚期NSCLC患者接受PD-1抑制剂一线免疫治疗较二线免疫治疗具有更好的临床治疗效果;一线免疫治疗患者外周血M-MDSCs显著下降,与疗效相关,二线免疫治疗后Tregs显著增加,但与疗效无关。 |
关键词: 非小细胞肺癌 PD-1抑制剂 免疫治疗 单核细胞-髓系来源抑制性细胞 粒细胞-髓系来源抑制性细胞 调节性T细胞 |
DOI:10.12025/j.issn.1008-6358.2021.20210511 |
分类号:R734.2 |
基金项目:国家自然科学基金(81870062,81900038). |
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Clinical efficacy of first-line and second-line immunotherapy in patients with non-small cell lung cancer and their effects on peripheral immunosuppressive activity |
FENG Jiu-xing1,2, CHEN Shu-jing1, ZHENG Tian-qi1, LI Shuang-qi2, LI Jia-min1, JIANG Jin-jun1
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1.Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China;2.Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Abstract: |
Objective: To explore the effects and impacts on peripheral blood immunosuppressive cell of first-line and second-line immunotherapy on non-small cell lung cancer (NSCLC). Methods: From January 2018 to October 2019, 27 patients with NSCLC were selected from Zhongshan Hospital, Fudan University. Seven were treated with first-line immunotherapy with PD-1 inhibitors, and 20 were treated with second-line immunotherapy. The clinical efficacy of PD-1 inhibitor first-line and second-line immunotherapy in 27 patients with NSCLC were analyzed, and the effects of different therapies on the main immune suppressor cells in peripheral blood including monocytic myeloid-derived suppressor cells (M-MDSCs), granulocytic myeloid-derived suppressor cells (G-MDSCs), and regulatory T cells (Tregs) were examined. Results: Among the first-line immunotherapy patients, 57.1% (4/7) had partial response (PR), 28.6% (2/7) had stable disease (SD), and 14.3% (1/7) had progressive disease (PD). Among the second-line immunotherapy patients, 15% (3/20) had PR, 55% (11/20) had SD, and 30% (6/20) had PD. Flow cytometry analysis showed that M-MDSCs in the first-line PD-1 inhibitor treatment group decreased significantly after the treatment, while there was no significant change in the second-line immunotherapy group. Furthermore, after the first cycle treatment, the first-line treatment group had lower levels of M-MDSCs than the second-line treatment group (P<0.05), indicating lower immunosuppressive activity caused by M-MDSCs in the former group, whereas there was no corresponding change in G-MDSCs. In contrast, the level of Tregs increased significantly in both groups, especially in the second-line immunotherapy group. Moreover, the correlation analysis proved that the decline of M-MDSCs was related to the therapeutic effect (r=-0.04, P<0.05), while the Tregs increase was not. Conclusions: Patients with advanced NSCLC receiving first-line immunotherapy have a better clinical therapeutic effect and lower level of immunosuppressive activity in the peripheral microenvironment than those receiving second-line immunotherapy. |
Key words: non-small cell lung cancer PD-1 inhibitor immunotherapy monocytic myeloid-derived suppressor cell granulocytic myeloid-derived suppressor cell regulatory T cell |