Xing Y F, Pan X, Qian B, Shi M H
Department of Respiratory Diseases, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Zhonghua Yi Xue Za Zhi. 2019 Jan 8;99(2):111-114. doi: 10.3760/cma.j.issn.0376-2491.2019.02.007.
To investigate the expression of programmed death 1(PD-1) and programmed death ligand 1 (PD-L1) on T lymphocyte and monocyte from peripheral blood of advanced non-small-cell lung cancer (NSCLC) patients and its potential role in immune escape of NSCLC. Forty-eight patients with advanced NSCLC (Lung Cancer Group) were included from the Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow University from June 2014 to June 2015. Thirty-six healthy volunteers who received health examination at the same time, matching in sex, age were also enrolled as controls. The expression of PD-1 on peripheral blood CD4(+)T cells and CD8(+)T cells and PD-L1 on monocytes were detected by flow cytometry. Patients who received chemotherapy alone for 2-4 cycles and received sequential sampling were assessed with Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Seven cases of patients with significant response to treatment were selected as partial response (PR) group and ten patients with poor response to treatment were treated as progression disease(PD) group. The differences in the expression of PD-1 on the surface of CD4(+)T cells, CD8(+)T cells, and PD-L1 on the surface of monocyte before and after treatment were analyzed. Compared with healthy control group, PD-1 expression level on both CD4(+) T and CD8(+) T cells from peripheral blood in lung cancer group were significantly increased [(25.9±7.4)% vs (20.6±6.2)%, (19.9±9.8)% vs (14.0±5.6)%, both 0.05]. A higher level of PD-L1 expression on monocyte in lung cancer group was also found compared with the control group [(33.1±15.1)% vs (13.6±5.3)%, 0.001]. The expression level of PD-1 on CD4(+)T and CD8(+)T cells and PD-L1 on monocytes in lung cancer group with good response to treatment was relatively lower than the baseline level of before treatment [(22.8±8.5)% vs (25.9±7.8)%, (17.1±8.4)% vs (20.4±8.6)%, (18.1±6.9)% vs (31.3±13.2)%, all 0.05], but in lung cancer group with poor response to treatment, it was higher than the baseline level of before treatment [(33.5±6.5)% vs (23.9±4.2)%, (25.2±9.1)% vs (19.1±8.8)%, (43.1±18.3)% vs (29.7±10.6)%, all 0.05]. Abnormal expression of PD-1 and PD-L1 exists in T cells and monocytes respectively, prompting PD-1/PD-L1 pathway may inhibit T cell proliferation during the interaction of T cell and monocyte, which may lead to non-small cell lung cancer immune escape.
探讨晚期非小细胞肺癌（NSCLC）患者外周血T淋巴细胞和单核细胞上程序性死亡蛋白1（PD-1）和程序性死亡配体1（PD-L1）的表达情况及其在NSCLC免疫逃逸中的潜在作用。选取2014年6月至2015年6月苏州大学附属第二医院呼吸内科收治的48例晚期NSCLC患者（肺癌组）。同时选取36例同期进行健康体检、性别和年龄匹配的健康志愿者作为对照组。采用流式细胞术检测外周血CD4(+)T细胞和CD8(+)T细胞上PD-1的表达以及单核细胞上PD-L1的表达。对接受2 - 4周期单纯化疗并进行序贯采样的患者，按照实体瘤疗效评价标准1.1（RECIST 1.1）进行评估。选取7例治疗反应显著的患者作为部分缓解（PR）组，10例治疗反应差的患者作为疾病进展（PD）组。分析治疗前后CD4(+)T细胞、CD8(+)T细胞表面PD-1以及单核细胞表面PD-L1表达的差异。与健康对照组相比，肺癌组外周血CD4(+)T细胞和CD8(+)T细胞上PD-1表达水平均显著升高[（25.9±7.4）%比（20.6±6.2）%，（19.9±9.8）%比（14.0±5.6）%，P均<0.05]。与对照组相比，肺癌组单核细胞上PD-L1表达水平也较高[（33.1±15.1）%比（13.6±5.3）%，P<0.001]。治疗反应良好的肺癌组中，CD4(+)T细胞、CD8(+)T细胞上PD-1以及单核细胞上PD-L1的表达水平相对低于治疗前基线水平[（22.8±8.5）%比（25.9±7.8）%，（17.1±8.4）%比（20.4±8.6）%，（18.1±6.9）%比（31.3±13.2）%，P均<0.05]，但治疗反应差的肺癌组中，其表达水平高于治疗前基线水平[（33.5±6.5）%比（23.9±4.2）%，（25.2±9.1）%比（19.1±8.8）%，（43.1±18.3）%比（29.7±10.6）%，P均<0.05]。PD-1和PD-L1分别在T细胞和单核细胞中存在异常表达，提示PD-1/PD-L1通路在T细胞与单核细胞相互作用过程中可能抑制T细胞增殖，这可能导致非小细胞肺癌免疫逃逸。
