一线和二线免疫治疗对非小细胞肺癌患者外周血免疫抑制细胞的影响

Clinical efficacy of first-line and second-line immunotherapy in patients with non-small cell lung cancer and their effects on peripheral immunosuppressive activity

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。

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.