程序性死亡受体-1与淋巴细胞活化基因-3在滤泡性淋巴瘤中的表达及临床意义

Expression and clinical significance of programmed death receptor-1 and lymphocyte activation gene-3 in follicular lymphoma

目的探讨程序性死亡受体-1(PD-1)、淋巴细胞活化基因-3(LAG-3)在滤泡性淋巴瘤(FL)肿瘤微环境中的表达情况及临床意义。方法选取2017—2022年中国科学技术大学附属第一医院22例病理明确诊断为FL的患者,采用免疫组化方法检测FL患者标本中PD-1、LAG-3、细胞程序性死亡-配体1(PD-L1)、细胞表面趋化因子受体4(CCR4)、细胞表面趋化因子受体3B(CXCR3B)、叉头蛋白P3抗体(FOXP3)因子的表达水平,分析PD-1、LAG-3与FL患者临床病理特征及预后的关系,并分析各因子间的相关性。结果PD-1高表达组和LAG-3高表达组β2微球蛋白(β_(2)-MG)水平高于低表达组,差异有统计学意义(P<0.05);PD-1/LAG-3双高表达组乳酸脱氢酶(LDH)和β2-MG水平高于PD-1/LAG-3单高表达组与PD-1/LAG-3双低表达组,差异有统计学意义(P<0.05)。相关性分析显示在FL组织中,PD-1表达水平与LAG-3、CCR4、CXCR3B表达水平呈正相关(r=0.432、0.440、0.506,P<0.05),而与PD-L1和FOXP3表达水平无相关性(P>0.05)。PD-1高表达组、LAG-3高表达组和PD-1/LAG-3共同高表达组CD8^(+)T细胞计数少于对应低表达组,差异有统计学意义(P<0.05),进一步相关性分析结果显示PD-1表达、LAG-3表达以及PD-1/LAG-3共同表达与CD8^(+)T细胞计数呈负相关(r=-0.631、-0.425、-0.552,P<0.05)。生存分析结果显示LDH低表达组的无进展生存期(PFS)和总体生存期(OS)优于高表达组;PD-1低表达组、LAG-3低表达组和PD-1/LAG-3双低表达组的PFS和OS优于高表达组,差异有统计学意义(P<0.05)。结论PD-1、LAG-3高表达与FL患者较高的临床检验指标水平及较差的生存预后相关;PD-1、LAG-3等免疫检查点在肿瘤微环境中共同表达,影响T细胞计数。

Objective To investigate the expression and clinical significance of programmed death receptor-1(PD-1)and lymphocyte activation gene-3(LAG-3)in the tumor microenvironment of follicular lymphoma(FL).Methods A total of 22 patients with FL diagnosed by pathology in the First Affiliated Hospital of University of Science and Technology of China from 2017 to 2022 were included.The expression levels of PD-1,LAG-3,programmed cell death-ligand 1(PD-L1),cell surface chemokine receptor 4(CCR4),cell surface chemokine receptor 3B(CXCR3B)and forkhead protein P3 antibody(FOXP3)in FL patients were detected by immunohistochemistry.The relationship between PD-1,LAG-3 and clinicopathological features and prognosis of FL patients was analyzed,and the correlation between each factor was analyzed.Results The levels ofβ2 microglobulin(β_(2)-MG)in PD-1 high expression group and LAG-3 high expression group were higher than those in low expression group,and the differences were statistically significant(P<0.05).The levels of lactate dehydrogenase(LDH)andβ2-MG in PD-1/LAG-3 double high expression group were higher than those in PD-1/LAG-3 single high expression group and PD-1/LAG-3 double low expression group,and the differences were statistically significant(P<0.05).Correlation analysis showed that in FL tissues,the expression level of PD-1 was positively correlated with the expression levels of LAG-3,CCR4 and CXCR3B(r=0.432,0.440,0.506,P<0.05),but not with the expression levels of PD-L1 and FOXP3(P>0.05).The CD8^(+)T cell count in PD-1 high expression group,LAG-3 high expression group and PD-1/LAG-3 co-high expression group was less than that in the corresponding low expression group,and the differences were statistically significant(P<0.05).Further correlation analysis results showed that PD-1 expression,LAG-3 expression and PD-1/LAG-3 co-expression were negatively correlated with CD8^(+)T cell count(r=-0.631,-0.425,-0.552,P<0.05).The results of survival analysis showed that the progression-free survival(PFS)and overall survival(OS)of LDH low expression group were better than those of LDH high expression group,and the PFS and OS of PD-1 low expression group,LAG-3 low expression group and PD-1/LAG-3 double low expression group were better than those of high expression group,and the differences were statistically significant(P<0.05).Conclusion The high expression of PD-1 and LAG-3 is related to the higher level of clinical test indexes and poor survival prognosis of FL patients.Immune checkpoints such as PD-1 and LAG-3 are co-expressed in the tumor microenvironment and affect T cell counts.