治疗前后外周血程序性死亡受体1^(+)CD8^(+)T淋巴细胞水平变化及其与非小细胞肺癌患者免疫治疗反应性的相关性

Changes of programmed death receptor 1^(+)CD8^(+)T lymphocyte levels in peripheral blood before and after treatment and its correlation with immunotherapy reactivity in patients with non-small cell lung cancer

目的 探讨治疗前后外周血程序性死亡受体1(PD-1)^(+)CD8^(+)T淋巴细胞水平变化与非小细胞肺癌(NSCLC)患者免疫治疗反应性的相关性。方法 将109例NSCLC患者根据疗效分为疾病控制组(DC组,75例)及疾病进展组(PD组,34例),收集其一般资料、临床资料、治疗前后T细胞占比、T细胞占比差值、比值、变化率及临床疗效并进行组间比较。相关因素分析采用多因素logistic回归分析。采用受试者工作特征(ROC)曲线评估相关因素对NSCLC患者免疫治疗反应性的预测价值。结果 DC组程序性死亡配体1(PD-L1)<1%比例低于PD组,而PD-L1>50%比例高于PD组;治疗后DC组CD3^(+)T细胞占比高于同组治疗前及同期PD组,而PD-1^(+)CD8^(+)T细胞占比均低于同组治疗前及同期PD组;DC组患者治疗前后PD-1^(+)CD8^(+)T细胞占比差值、比值及变化率均低于同期PD组(P<0.05)。多因素logistic回归分析结果显示,PD-1^(+)CD8^(+)T细胞占比治疗前后变化率及PD-L1是影响NSCLC患者免疫治疗反应性的独立危险因素(P<0.05)。ROC曲线分析结果显示,PD-1^(+)CD8^(+)T细胞治疗前后变化率联合PD-L1对NSCLC患者免疫治疗反应性具有一定的预测价值(P<0.001)。结论 PD-1^(+)CD8^(+)T细胞动态变化情况与NSCLC患者免疫治疗反应性具有显著的相关性。

Objective To explore the correlation between changes of programmed death receptor 1(PD-1)^(+)CD8^(+)T lymphocytes in peripheral blood and immunotherapy reactivity in patients with non-small cell lung cancer(NSCLC) before and after treatment.Methods A total of 109 NSCLC patients were divided into disease control(DC) group(75 cases) and disease progression(PD) group(34 cases) according to the efficacy.General data,clinical data,T lymphocyte proportion,T lymphocyte proportion difference,ratio and change rate before and after treatment,clinical efficacy were collected and compared between groups.The correlation factors were analyzed by multi-factor logistic regression analysis.Receiver operating characteristics(ROC) curve was used to assess the predictive value of relevant factors for immunotherapy responsivenes in patients with NSCLC.Results The proportion with programmed death ligand 1(PD-L1)<1% in DC group was lower than that in PD group,while the proportion with PD-L1>50% was higher than that in PD group;After treatment,the proportion of CD3^(+)T lymphocytes in DC group was higher than that before treatment and PD group at the same period,while the proportion of PD-1^(+)CD8^(+)T lymphocytes was lower than that before treatment and PD group at the same period;The proportion difference,ratio and change rate of lymphocytes in PD-1^(+)CD8^(+)T before and after treatment in DC group were lower than those in PD group(P<0.05).Multivariate logistic regression analysis showed that the change rate of PD-1^(+)CD8^(+)T lymphocyte ratio before and after treatment and PD-L1 were independent risk factors affecting immunotherapy reactivity in NSCLC patients(P<0.05).ROC curve analysis showed that the change rate of PD-1^(+)CD8^(+)T lymphocytes before and after treatment combined with PD-L1 had a certain predictive value for immunotherapy responsiveness in NSCLC patients(P<0.001).Conclusion The dynamic changes of PD-1^(+)CD8^(+)T cells were significantly correlated with immunotherapy responsiveness in NSCLC patients.