中晚期癌症患者抗PD-1单抗治疗前后PD-1、CTLA-4和Ki-67的变化与疗效的关系

The relationship between the change tendency of expression of PD-1,CTLA-4 and Ki-67 and response of anti-PD-1 therapy in mid-advanced cancer patients

目的:探究中晚期癌症患者抗PD-1单抗治疗前后抑制性免疫检查点的变化与疗效的关系。方法:采集22例将接受抗PD-1单抗治疗中晚期癌症患者的外周血,于每次免疫治疗前收集,每人至少3次。通过流式细胞的方法检测PD-1、CTLA-4和Ki-67在T淋巴细胞上的表达情况。结果:通过两周期评价结果将患者分为有效组和无效组,组间比较发现PD-1、CTLA-4和Ki-67表达有统计学意义;绘制变化趋势图发现PD-1和Ki-67在有效组有先上升后下降的趋势,CTLA-4在无效组有持续上升的趋势。结论:通过动态检测抑制性免疫检查点分析其变化趋势与早期患者免疫治疗疗效相关。

Objective： In this study,we try to find out the relationship between the clinical benefit and the change of negative immune biomarkers on peripheral blood monocular cells（ PBMCs） by continuous testing. Methods： Twenty-two patients diagnosed as advanced malignant cancer received nivolumab or pembrolizumab. We performed flow cytometry analysis of peripheral blood samples to test negative immune checkpoint molecules： PD-1,CTLA-4 and Ki-67. Blood draws are obtained before and after treatment at least three times. Results： Comparing response group and non-response group,we found that the change of expression of PD-1,CTLA-4 and Ki-67 was meaningful（ P＜0. 05）. By processing the data and drawing diagram we found that elevation of key biomarkers after the first cycle of immunotherapy,followed by a decrease in expression after the second cycle,was associated with better benefits from immunotherapy at early stage. Conclusion： The clinical benefits after the treatment of anti-PD-1 agents relate to the change of expression of negative immune checkpoints,which may be the response index to predict immunotherapy.