淋巴细胞亚群对晚期非小细胞肺癌患者化疗效果及远期生存的影响

Impact of Lymphocyte Subsets on Chemotherapy Efficacy and Long-term Survival of Patients with Advanced Non-small-cell Lung Cancer

目的评估淋巴细胞亚群对晚期非小细胞肺癌(NSCLC)患者化疗效果及远期生存的影响。方法以125例接受紫杉醇±铂类、培美曲塞±铂类或其他一线化疗方案的晚期NSCLC患者为研究对象,采用流式细胞仪检测化疗前及化疗2个周期后的外周血21项淋巴细胞亚型的表达情况,根据影像学检查结果评价化疗疗效,分析淋巴细胞亚群对患者疗效和无进展生存时间(PFS)及总生存时间(OS)的影响。结果不同化疗疗效组患者化疗前的淋巴细胞亚群间差异均无统计学意义(P均>0.05);2周期化疗后,完全缓解(CR)+部分缓解(PR)组、疾病稳定(SD)组和疾病进展(PD)组患者的CD4+CD29+细胞百分比分别为(22.42±7.88)%、(21.88±6.81)%和(16.87±5.28)%,其中,PD组明显低于CR+PR组(P=0.013)和SD组(P=0.009)。中位PFS为7.07个月,中位OS为23.00个月。COX多因素回归分析结果显示,化疗前HLA-DR+细胞(HR:1.03,95%CI:1.01~1.05,P<0.001)及CD3+HLA-DR+细胞(HR:1.05,95%CI:1.01~1.08,P<0.001)表达水平与患者的OS呈显著正相关。结论化疗后CD4+CD29+T淋巴细胞水平升高可能提示患者的化疗效果较好。化疗前HLA-DR+细胞及CD3+HLA-DR+细胞在外周血中所占百分比越高,可能提示患者的预后越好。

Objective To analyze the impact of lymphocyte subsets on chemotherapy efficacy and longterm survival of patients with advanced non-small cell lung cancer（NSCLC）. Methods Totally 125 NSCLCpatients who had received first-line chemotherapy including paclitaxel and pemetrexed with/without platinum were enrolled in this study. Lymphocytes from peripheral blood were collected before and after two cycles of first-line chemotherapy. Flow cytometry was performed to determine the expressions of 21 fluorescence-labeled lymphocyte subsets. Based on the imaging findings,chemotherapy efficacy was evaluated,and impact of the lymphocyte subsets on progression-free survival（PFS） and overall survival（OS） were analyzed. Results The baseline peripheral lymphocyte subsets showed no significant difference among groups receiving different treatment protocols（all P〈0. 05）. After 2 cycles of chemotherapy,the percentage of CD4＋CD29＋lymphocytes was（16. 87 ±5. 28） % in progressive disease group,which was significantly lower than those in complete remission ＋ partial remission group [（22. 42 ± 7. 88） %,P = 0. 013]and stable disease group [（21. 88 ± 6. 81） %,P = 0. 009]. The median PFS was 7. 07 months and median OS was 23. 00 months. Cox multivariable regression analysis showed that the percentages of HLA-DR＋（HR： 1. 03,95% CI： 1. 01-1. 05,P〈0. 001） and CD3 ＋HLA-DR＋lymphocytes（HR： 1. 05,95% CI： 1. 01-1. 08,P〈0. 001） were positively correlated with OS. Conclusions The rise of CD4＋CD29＋T lymphocytes in patients after chemotherapy indicates good chemotherapy efficacy. Higher percentage of HLA-DR＋and CD3＋HLA-DR＋lymphocytes in peripheral blood before chemotherapy predicts favorable prognosis.