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.
题目: 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.
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.
Keywords: flow cytometry; multiple myeloma; programmed death receptor 1; regulatory T cells.