王晓丽　　江妤　　曾玉晓　　刘永华　　章俏雷

[關键词] CD4+ CD25+ FOXP3+;调节性T淋巴细胞;高危;多发性骨髓瘤;化疗;疗效;复发

[中图分类号] R733.3          [文献标识码] A          [文章编号] 1673-9701（2021）16-0032-05

Significance of CD4+ CD25+ FOXP3+ Treg cells in predicting recurrence and therapeutic effect in treatment of high-risk multiple myeloma

WANG Xiaoli   JIANG Yu   ZENG Yuxiao   LIU Yonghua   ZHANG Qiaolei

Department of Hematology，Lishui People′s Hospital in Zhejiang Province， Lishui   323000， China

[Abstract] Objective To explore the significance of CD4+ CD25+ FOXP3+ regulatory T lymphocytes （Treg） in predicting recurrence and therapeutic effect in the treatment of high-risk multiple myeloma. Methods A total of 126 patients with high-risk multiple myeloma admitted to our hospital from March 2018 to March 2019 were selected as the case group， and 100 healthy patients who received physical examination in our hospital during the same period were selected as the control group. The proportions of CD4+ CD25+ FOXP3+ Treg cells in the peripheral blood were compared between the case group and the control group，and among patients with different chemotherapy effect and recurrence conditions. Spearman correlation was used to analyze the correlation between the proportion of CD4+ CD25+ FOXP3+ Treg cells and the recurrence. Receiver operating characteristic curve （ROC） was used to analyze the value of the proportion of CD4+ CD25+ FOXP3+ Treg cells in predicting recurrence. Kaplan-Meier analysis was used to analyze the progression-free survival during follow-up of patients with different proportions of CD4+ CD25+ FOXP3+ Treg cells. Results The proportion of CD4+ CD25+ FOXP3+ Treg cells in the case group was significantly higher than that in the control group （P<0.001）. The proportion of CD4+ CD25+ FOXP3+ Treg cells in chemotherapy-ineffective patients was significantly higher than that in chemotherapy-effective patients（P<0.001）. The proportion of CD4+ CD25+ FOXP3+ Treg cells in patients with recurrence was significantly higher than that of patients without recurrence（P<0.001）. The proportion of CD4+ CD25+ FOXP3+ Treg cells was positively correlated with patient recurrence（P<0.05）. The AUC of the proportion of CD4+ CD25+ FOXP3+ Treg cells in predicting recurrence was 0.809 （95%CI： 0.759-0.856）， with sensitivity of 62.80%， specificity of 95.80%， accuracy of 89.30%， and cutoff value of 3.66%. The patients with CD4+ CD25+ FOXP3+ Treg cell ratio >3.66% had a significantly lower progression-free survival rate during follow-up than those with CD4+ CD25+ FOXP3+ Treg cell ratio <3.66%（P<0.05）. Conclusion The proportion of CD4+ CD25+ FOXP3+ Treg cells has an increasing trend in the peripheral blood of patients with high-risk multiple myeloma. The detection of its level has a certain predictive value for recurrence after chemotherapy，which is helpful for clinical prediction of chemotherapy effect， monitoring of early recurrence and prognostic judgment.

[Key words] CD4+ CD25+ FOXP3+; Regulatory T lymphocytes; High risk; Multiple myeloma; Chemotherapy; Therapeutic effect; Recurrence

多发性骨髓瘤是一种由浆细胞增殖异常所致的血液系统恶性肿瘤，目前以硼替佐米为主的化学药物治疗方案的临床疗效获得肯定，但该病的复发仍是一大难题，特别相较于低危患者，高危患者预后差异性明显，其中肿瘤免疫逃逸扮演了重要角色[1-2]。CD4+ CD25+ FOXP3+ 调节性T细胞（Treg）作为肿瘤免疫逃逸的重要调控因素，在多发性骨髓瘤发病和病情进展过程中发挥重要作用[3-4]。Treg细胞的增加可使机体抗肿瘤免疫系统受损，造成肿瘤免疫逃逸和肿瘤进展。现已发现，在多发性骨髓瘤患者发病过程中肿瘤微环境Treg细胞比例异常增加，其增加程度因个体与疾病阶段而异，且Treg细胞与多发性骨髓瘤更高的进展风险关系密切[5]，这与即将要重点研究的高危多发性骨髓瘤患者方向一致。本研究分析了CD4+ CD25+ FOXP3+ Treg细胞在高危多发性骨髓瘤治疗中预测复发的意义，希望为高危多发性骨髓瘤的临床治疗和预后指导提供依据，现报道如下。

1 资料与方法

1.1一般资料

征得我院医学伦理委员会批准，选择2018年3月至2019年3月我院收治的126例高危多发性骨髓瘤患者为病例组，同期在我院体检健康者100例为对照组。病例组男87例，女39例;年龄30～75岁，平均（56.20±4.85）岁;体质量指数（22.41±2.23）kg/m2;Durie-Salmon（D-S）分期：Ⅰ期3例，Ⅱ期16例，Ⅲ期107例;国际分期系统（ISS）分期：Ⅰ期14例，Ⅱ期67例，Ⅲ期45例。对照组男62例，女38例;年龄30～78岁，平均（55.29±5.07）岁;体质量指数（22.17±2.92）kg/m2。两组一般资料比较，差异无统计学意义（P>0.05），具有可比性。纳……