Expression of programmed death-1/programmed death-ligand 1 in chronic lymphocytic leukemia patients and its correlation with T lymphocyte subsets

doi:10.3969/j.issn.1673-8640.2025.06.013

Abstract

Abstract:

Objective To investigate the expression of programmed death-1（PD-1）/programmed death-ligand 1（PD-L1） in chronic lymphocytic leukemia（CLL） patients and its correlation with T lymphocyte subsets，and to provide a reference for targeted intervention of CLL. Methods Totally，70 patients with CLL in Jinhua People's Hospital from April 2020 to June 2023 were enrolled as CLL group，and the patients were classified into Group A（24 cases），Group B（30 cases） and Group C（16 cases） according to Binet classification. Another 49 patients with chronic myelogenous leukemia in Jinhua People's Hospital were enrolled as control group. The PD-1 mRNA，PD-L1 mRNA and T lymphocyte subsets were determined. Multivariate Logistic regression analysis was used to investigate the relationship between CLL and PD-1 mRNA，PD-L1 mRNA. Pearson correlation analysis was used to evaluate the correlation between PD-1 mRNA，PD-L1 mRNA and T lymphocyte subsets. Results Compared with control group，the expressions of PD-1 mRNA，PD-L1 mRNA，T helper cell（Th）9 and Th17 in CLL group were increased（P<0.05），while the expression of Treg was decreased（P<0.05）. The levels of PD-1 mRNA，PD-L1 mRNA，Th9 and Th17 in Group A，B and C were increased，and Treg was decreased gradually（P<0.05）. PD-1 mRNA，PD-L1 mRNA，Th9 and Th17 increasing and Treg decreasing were independent influencing factors for CLL（P<0.05）. PD-1 mRNA，PD-L1 mRNA were negatively correlated with Treg, and PD-1 mRNA，PD-L1 mRNA were positively correlated with Th9 and Th17（P<0.05）. Conclusions The expressions of PD-1 mRNA，PD-L1 mRNA are increased in CCL，which can be used to predict CCL，providing a reference for clinical diagnosis.

Key words: Programmed death-1, Programmed death-ligand 1, Chronic lymphocytic leukemia, T lymphocyte subset

CLC Number:

R446.62

SHI Fangjing, HU Shanshan, LUO Xinguo, ZHU Yan, YU Fangquan, YE Hongwei. Expression of programmed death-1/programmed death-ligand 1 in chronic lymphocytic leukemia patients and its correlation with T lymphocyte subsets[J]. Laboratory Medicine, 2025, 40(6): 592-595.

Figures/Tables 5

References 21

[1]	荆源, 林樉, 王芳婷, 等. 荧光原位杂交技术检测43例慢性淋巴细胞白血病患者基因异常[J]. 中国实验血液学杂志, 2018, 26(4):1038-1043.
[2]	曹丹, 方遒, 张宗新. 干扰素调节因子3基因多态性检查在慢性淋巴细胞白血病患者中的预后价值[J]. 中国卫生检验杂志, 2017, 27(2):227-231.
[3]	闫楠楠, 张纯, 孙敏. 维奈克拉联合用药治疗慢性淋巴细胞白血病的研究进展[J]. 医学理论与实践, 2021, 34(23):4070-4072.
[4]	GRZYWNOWICZ M, KARCZMARCZYK A, SKORKA K, et al. Expression of programmed death 1 ligand in different compartments of chronic lymphocytic leukemia[J]. Acta Haematol, 2015, 134(4):255-262.
[5]	HE R, DING W, VISWANATHA D S, et al. PD-1 expression in chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL) and large B-cell Richter transformation(DLBCL-RT):a characteristic feature of DLBCL-RT and potential surrogate marker for clonal relatedness[J]. Am J Surg Pathol, 2018, 42(7):843-854.
[6]	中国抗癌协会血液肿瘤专业委员会, 中华医学会血液学分会,中国慢性淋巴细胞白血病工作组. 中国慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的诊断与治疗指南(2022年版)[J]. 中华血液学杂志, 2022, 43(5):353-358.
[7]	薛超, 杨凡, 管莎莎, 等. 肺癌PD-1/PD-L1抑制剂治疗的耐药机制[J]. 肿瘤综合治疗电子杂志, 2022, 8(4):105-113.
[8]	黄林, 何娟. PD-1/PD-L1抑制剂与前列腺癌免疫治疗的研究进展[J]. 中华男科学杂志, 2020, 26(10):944-948.
[9]	DORFMAN D M, BROWN J A, SHAHSAFAEI A, et al. Programmed death-1(PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma[J]. Am J Surg Pathol, 2006, 30(7):802-810.
[10]	TKACHEV V, GOODELL S, OPIPARI A W, et al. Programmed death-1 controls T cell survival by regulating oxidative metabolism[J]. J Immunol, 2015, 194(12):5789-5800. DOI PMID
[11]	DOLAN D E, GUPTA S. PD-1 pathway inhibitors:changing the landscape of cancer immunotherapy[J]. Cancer Control, 2014, 21(3):231-237.
[12]	姚满, 周艳楠, 曹启江. 调节性T细胞外泌体对肿瘤调节作用的研究进展[J]. 免疫学杂志, 2019, 35(11):1009-1012.
[13]	张亚楠, 季旭明, 王世军. 中药干预肿瘤调节性T细胞的作用及机制研究进展[J]. 医学研究杂志, 2018, 47(10):11-12.
[14]	XIE Q, TANG Z, LIANG X, et al. An immune-related gene prognostic index for acute myeloid leukemia associated with regulatory T cells infiltration[J]. Hematology, 2022, 27(1):1088-1100. DOI PMID
[15]	JABEEN R, GOSWAMI R, AWE O, et al. Th9 cell development requires a BATF-regulated transcriptional network[J]. J Clin Invest, 2013, 123(11):4641-4653.
[16]	GOSWAMI R, JABEEN R, YAGI R, et al. STAT6-dependent regulation of Th9 development[J]. J Immunol, 2012, 188(3):968-975. DOI PMID
[17]	KUMAR S, DHAMIJA B, MARATHE S, et al. The Th9 axis reduces the oxidative stress and promotes the survival of malignant T Cells in cutaneous T-Cell lymphoma patients[J]. Mol Cancer Res, 2020, 18(4):657-668. DOI PMID
[18]	马婷婷, 李娟. Th17细胞在弥漫大B细胞淋巴瘤中的研究进展[J]. 临床血液学杂志, 2017, 30(7):564-567.
[19]	张庆, 郭明洲. 胰腺癌免疫治疗及超进展的研究现状和思考[J]. 胃肠病学和肝病学杂志, 2021, 30(7):726-729.
[20]	苏艳丽, 李波. Th9细胞对非小细胞肺癌患者CD8+T细胞抗肿瘤活性的调控作用[J]. 陕西医学杂志, 2021, 50(1):15-21.
[21]	秦琪, 刘朝奇, 熊焱强, 等. PD-1/PD-L1信号通路及相关抗体在宫颈癌免疫治疗中的应用[J]. 生命的化学, 2017, 37(6):992-997.

基因名称	上游引物（5'~3'）	下游引物（5'~3'）
PD-1	TGGCATGTGCCAGATCATTTG	CCTTGCAGCTATTGTAGCAAACC
PD-L1	TGCTTAACGCCTTGGAAGA	CCAGCACACTTGTCCTTCA
GAPDH	GCACCGTCAAGGCTGAGAAC	TGGTGAAGACGCCAGTGGA

基因名称	上游引物（5'~3'）	下游引物（5'~3'）
PD-1	TGGCATGTGCCAGATCATTTG	CCTTGCAGCTATTGTAGCAAACC
PD-L1	TGCTTAACGCCTTGGAAGA	CCAGCACACTTGTCCTTCA
GAPDH	GCACCGTCAAGGCTGAGAAC	TGGTGAAGACGCCAGTGGA

组别	例数	PD-1 mRNA	PD-L1 mRNA	Treg/%	Th9/%	Th17/%
CLL组	70	1.75±0.40	1.64±0.38	4.25±1.02	1.30±0.35	2.08±0.48
对照组	79	1.04±0.24	1.05±0.23	7.54±2.21	0.68±0.23	1.04±0.33
t值		11.097	9.690	10.918	10.860	13.140
P值		<0.001	<0.001	<0.001	<0.001	<0.001

组别	例数	PD-1 mRNA	PD-L1 mRNA	Treg/%	Th9/%	Th17/%
CLL组	70	1.75±0.40	1.64±0.38	4.25±1.02	1.30±0.35	2.08±0.48
对照组	79	1.04±0.24	1.05±0.23	7.54±2.21	0.68±0.23	1.04±0.33
t值		11.097	9.690	10.918	10.860	13.140
P值		<0.001	<0.001	<0.001	<0.001	<0.001

组别	例数	PD-1 mRNA	PD-L1 mRNA	Treg/%	Th9/%	Th17/%
A组	24	1.41±0.35	1.35±0.33	6.14±1.59	1.04±0.26	1.64±0.39
B组	30	1.79±0.42	1.71±0.39	4.35±1.08	1.35±0.31	2.05±0.41
C组	16	2.11±0.45	2.01±0.43	3.21±0.57	1.76±0.41	2.57±0.50
t值		14.888	15.005	30.773	24.332	23.012
P值		<0.001	<0.001	<0.001	<0.001	<0.001