弥漫大B细胞淋巴瘤患者外周血T淋巴细胞亚群变化及其临床意义

Changes of T lymphocyte subsets in peripheral blood of patients with diffuse large B-cell lymphoma and its clinical significance

目的探讨弥漫大B细胞淋巴瘤(DLBCL)患者外周血中T淋巴细胞亚群的变化及其临床意义。方法回顾性分析2022年1月至2023年1月厦门大学附属第一医院收治的99例DLBCL患者临床资料。采用流式细胞术检测患者治疗前后外周血中T淋巴细胞亚群。根据患者采血检测时的疾病状态分为初诊DLBCL组(28例)及初治缓解后DLBCL组(71例),选取同期40名健康体检者作为健康对照组,比较3组间T淋巴细胞及相关亚群比例和绝对值的差异。分析初诊DLBCL患者T淋巴细胞各亚群间相关性,及各亚群与国际预后指数(IPI)评分、治疗反应的相关性。结果初诊DLBCL组CD3^(+)T细胞比例较健康对照组降低[(58±14)%比(67±7)%,P<0.05];初诊及初治缓解后DLBCL组CD3^(+)T细胞绝对值较健康对照组均降低[(875±483)/μl、(808±553)/μl比(1374±279)/μl,均P<0.001]。初诊DLBCL组CD4^(+)T及CD8^(+)T细胞绝对值较健康对照组均降低[(478±313)/μl比(695±154)/μl,(316±181)/μl比(525±193)/μl,均P<0.001];初治缓解后DLBCL组CD4^(+)T细胞比例及绝对值与初诊DLBCL组、健康对照组比较均降低[(40±14)%比(53±14)%、(51±9)%,(313±247)/μl比(478±313)/μl、(695±154)/μl,均P<0.05],CD8^(+)T细胞比例较另外两组均升高[(51±15)%比(37±12)%、(38±9)%,均P<0.001]。与健康对照组比较,初诊及初治缓解后DLBCL组调节性T细胞(Treg)和常规T细胞(Tcon)的效应、记忆亚群比例均升高[(79±16)%、(84±12)%比(71±11)%,(72±16)%、(76±14)%比(62±13)%,均P<0.05],CD127^(+)记忆Tcon和CD8^(+)T细胞亚群比例均降低[(73±14)%、(66±20)%比(85±8)%,(39±15)%、(25±21)%比(62±16)%,均P<0.05]。在初诊DLBCL组中,CD3^(+)T细胞和CD4^(+)T细胞的绝对值与效应Treg比例均呈负相关(r=-0.379,P=0.049;r=-0.384,P=0.040);IPI评分分组与CD8^(+)T细胞比例相关(Eta2=0.15,P=0.038);治疗后非完全缓解组较完全缓解组CD127^(+)记忆Tcon升高(P=0.020)。结论初诊DLBCL患者外周血T淋巴细胞比例及绝对值均降低,分化状态发生改变,且与患者临床特征及治疗反应相关。DLBCL治疗缓解后T淋巴细胞仍不能完全恢复至正常。

Objective To investigate the changes of T lymphocyte subsets in peripheral blood of patients with diffuse large B-cell lymphoma(DLBCL)and its clinical significance.Methods The clinical data of 99 DLBCL patients admitted to the First Affiliated Hospital of Xiamen University from January 2022 to January 2023 were retrospectively analyzed.T lymphocyte subsets in peripheral blood before and after treatment were detected by using flow cytometry.According to the disease status at the time of blood collection and detection,the patients were divided into the newly-diagnosed DLBCL group(28 cases),and the newly-treated remission DLBCL group(71 cases);and 40 healthy volunteers undergoing the physical examination during the same period were selected as the healthy control group.The proportion and absolute count differences of T lymphocytes and the related subsets in 3 groups were compared.Besides,the correlation among T lymphocyte subsets,the correlation of each subset with international prognostic index(IPI)score and treatment response in newly-diagnosed DLBCL patients were further analyzed.Results The proportion of CD3^(+)T cells in newly-diagnosed DLBCL group was decreased compared with that in the healthy control group[(58±14)%vs.(67±7)%,P<0.05].The absolute count of CD3^(+)T cells in both newly-diagnosed group and the newly-treated remission group was reduced compared with that in the healthy control group[(875±483)/μl and(808±553)/μl vs.(1374±279)/μl,P<0.001].The absolute count of CD4^(+)and CD8^(+)T cells in newly-diagnosed group was decreased compared with that in the healthy control group[(478±313)/μl vs.(695±154)/μl,(316±181)/μl vs.(525±193)/μl,all P<0.001].Both the proportion and absolute count of CD4^(+)T cells in the newly-treated remission DLBCL group were decreased compared with those in the newly-diagnosed DLBCL group and the healthy control group[(40±14)%vs.(53±14)%and(51±9)%,(313±247)/μl vs.(478±313)/μl and(695±154)/μl,all P<0.05].The porportion of CD8^(+)T cells was increased compared with that in the other two groups[(51±15)%vs.(37±12)%and(38±9)%,all P<0.001].Compared with the healthy control group,the effect/memory subsets proportion of regulatory T cell(Treg)and conventional T cell(Tcon)were increased in both newly-diagnosed DLBCL group and the newly-treated remission DLBCL group[(79±16)%and(84±12)%vs.(71±11)%,(72±16)%and(76±14)%vs.(62±13)%,all P<0.05],and the proportion of CD127^(+)memory Tcon and CD8^(+)T cell subsets was reduced[(73±14)%and(66±20)%vs.(85±8)%,(39±15)%and(25±21)%vs.(62±16)%,all P<0.05].In newly-diagnosed DLBCL group,the absolute counts of CD3^(+)T and CD4^(+)T cells were negatively correlated with the proportion of effector Treg(r=-0.379,P=0.049;r=-0.384,P=0.040,respectively).IPI score of DLBCL patients was correlated with the proportion of CD8^(+)T cells(Eta2=0.15,P=0.038).The proportion of CD127^(+)memory Tcon in patients with non-complete remission was increased compared with that in patients with complete remission after treatment(P=0.020).Conclusions The proportion and absolute count of T lymphocyte cells in peripheral blood of newly-diagnosed DLBCL patients is decreased,and the differentiation state of T lymphocyte cells shows change trend,which is related to the clinical characteristics and treatment response of DLBCL patients.Even if DLBCL patients have achieved treatment remission,T lymphocyte cells are not completely return to the normal.