结直肠癌患者外周血及肿瘤组织中PD-1/PD-L1及相关免疫细胞水平变化特点及临床意义

Changes and Clinical Significance of PD-1/PD-L1 and Related Immune Cells in Peripheral Blood and Tumor Tissues of Patients with Colorectal Cancer

目的 检测结直肠癌患者外周血及肿瘤组织内程序性死亡分子-1(PD-1)/PD-1配体(PD-L1)、相关免疫细胞表达水平,并分析其临床表达意义。方法 将80例行结直肠癌根治术患者纳为癌变组,同期80例健康体检合格者纳为对照组,采集2组外周静脉血,检测PD-1、PD-L1、CD4+CD25+调节性T细胞(CD4+CD25+Tregs)标志物叉状头/翅膀状螺旋转录因子(Foxp3)表达水平,术中收集结直肠癌患者癌灶及癌旁组织,免疫组化法检测癌灶及癌旁组织内PD-1、PD-L1及Foxp3蛋白表达水平。结果 癌变组患者外周血PD-1、PD-L1及Foxp3水平均高于对照组,差异均具有统计学意义(P<0.05)。癌变组患者术后外周血PD-1、PD-L1及Foxp3水平均较其术前下降,差异具有统计学意义(P<0.05)。结直肠癌组织中PD-1、PD-L1及Foxp3阳性表达率均高于癌旁组织,差异均存在统计学意义(P<0.05)。癌灶组织内PD-1阳性表达与肿瘤浸润深度、淋巴结转移及pTNM分期具有相关性(P<0.05);癌灶组织内PD-L1阳性表达与肿瘤部位、浸润深度具有相关性(P<0.05);Foxp3 Treg阳性表达与肿瘤分化程度、浸润深度及淋巴结转移具有相关性(P<0.05)。结论 PD-1、PD-L1及Treg细胞均与结直肠癌肿瘤免疫微环境相关,与结直肠癌发生及发展间均存在联系,三者联合检测可用于评估结直肠癌免疫检查点抑制剂的治疗新指标。

Objective To investigate the changes and clinical significance of programmed cell death protein 1(PD-1)/programmed cell death-ligand 1(PD-L1)and related immune cells in peripheral blood and tumor tissues of patients with colorectal cancer.Methods 80 patients underwent radical resection of colorectal cancer were included in cancer group,and another 80 healthy patients underwent physical examination during the same period were enrolled as the control group.Peripheral venous blood was collected from both groups.The expression levels of PD-1,PD-L1,CD4+CD25+regulatory T cells(CD4+CD25+Tregs)and fork head/winged helix transcription factor p3(Foxp3)were measured.The cancer tissues and adjacent normal tissues were collected during surgery,and the expression levels of PD-1,PD-L1 and Foxp3 proteins in the tumor tissues and adjacent tissues were detected by immunohistochemistry.Results The expression levels of PD-1,PD-L1 and Foxp3 in peripheral blood of cancer group were higher than those of the control group(P<0.05).After surgery,the expression levels of PD-1,PD-L1 and Foxp3 in peripheral blood were decreased in cancer group(P<0.05).The positive expression rates of PD-1,PD-L1 and Foxp3 in cancer tissues were higher than those in adjacent normal tissues(P<0.05).The positive expression of PD-1 in cancer tissues was correlated with the depth of tumor invasion,lymph node metastasis and pTNM stage(P<0.05).The positive expression of PD-L1 in cancer tissues was correlated with tumor location and depth of invasion(P<0.05).The positive expression of Foxp3 Treg was correlated with tumor differentiation,depth of invasion and lymph node metastasis(P<0.05).Conclusion PD-1,PD-L1 and Treg cells are all associated with the immune microenvironment of colorectal cancer and have been linked to the occurrence and development of colorectal cancer,and the combined detection of the three indicators can be used to evaluate the response to immune checkpoint inhibitors in colorectal cancer patients.