PD-1、PD-L1和CTLA-4在多发性骨髓瘤患者骨髓中的表达与意义

Expression and Significance of PD-1,PD-L1 and CTLA-4 in the Bone Marrow of Patients with Multiple Myeloma

目的:研究PD-1、PD-L1和CTLA-4肿瘤相关抗原在多发性骨髓瘤中的表达及意义。方法:收集多发性骨髓瘤患者骨髓标本122份,根据患者疾病的进展阶段分为新发(NDMM)、完全缓解(CRMM)和复发难治(RRMM)共3组。利用多参数流式细胞仪检测标本中CD4^(+)和CD8^(+)T淋巴细胞、Treg细胞和浆细胞(plasma cell,PC)的比例,并分析细胞中PD-1、PD-L1及CTLA-4的表达情况。结果:不同阶段MM患者间CD8^(+)T细胞比例和Treg细胞比例比较均无统计学差异(P>0.05),NDMM组CD4^(+)T细胞和PC的比例均显著高于CRMM组(P<0.05),NDMM和RRMM组CD4^(+)/CD8^(+)T比值均显著性高于CRMM组(P<0.05);CD8^(+)T细胞中PD-1、PD-L1和CTLA-4的表达在NDMM、CRMM和RRMM组组间比较均无显著性统计学差异(P>0.05);PC和CD4^(+)T细胞中PD-1、PD-L1和CTLA-4的表达在NDMM组显著低于CRMM组(P<0.05);Treg细胞中PD-1的表达在3组间存在显著性差异,NDMM组显著低于CRMM组(均P<0.05)。PD-1和CTLA-4在PC中的表达均显著性高于CD8^(+)T、CD4^(+)T和Treg细胞(均P<0.05);PD-L1在CD8^(+)T淋巴细胞中的表达显著高于CD4^(+)T淋巴细胞和Treg细胞(P<0.05)。结论:多发性骨髓瘤的免疫状态与体内浆细胞和各淋巴细胞亚群中PD-1、PD-L1及CTLA-4的表达情况存在相关关系。

Objective:To study the expression and significance of PD-1,PD-L1 and CTLA-4 tumor-associated antigens in multiple myeloma.Methods:Bone marrow specimens from 122 patients with multiple myeloma were collected and divided into new-onset group(NDMM),complete remission group(CRMM)and relapsed and refractory group(RRMM)according to the disease progression stage.The proportion of CD4^(+)T lymphocytes,CD8^(+)T lymphocytes,Treg cells and plasma cells in the specimens and the expressions of PD-1,PD-L1 and CTLA-4 were detected by multi-parameter flow cytometry.Results:There was no significant difference in the proportion of CD8^(+)T and Treg cells among the three groups(P>0.05),while the proportions of CD4^(+)T cells and PC in NDMM group were significantly higher than those in the CRMM group(P<0.05),the ratios of CD4^(+)to CD8^(+)T in the NDMM and RRMM groups were significantly higher than those in the CRMM group(P<0.05).The expressions of PD-1,PD-L1 and CTLA-4 in CD8^(+)T cells was no significant difference among NDMM,CRMM and RRMM groups(P>0.05).While the expressions of PD-1,PD-L1 and CTLA-4 in CD4^(+)T cells and PC in the NDMM group were significantly lower than that in the CRMM group(P<0.05).There was significantly difference among the three groups in the expression of PD-1 in Treg cells,of which the NDMM group was significantly lower than that of the CRMM group(all P<0.05).The expressions of PD-1 and CTLA-4 in PC were significantly higher than those in CD8^(+)T,CD4^(+)T and Treg cells(P<0.05),the expression of PD-L1 in CD8^(+)T cells was significantly higher than that in CD4^(+)T and Treg cells(P<0.05).Conclusion:There is a correlation between the immune status of multiple myeloma and the expressions of PD-1,PD-L1 and CTLA-4 in plasma cells and lymphocyte subsets in vivo.