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PD-1/PD-L1 在经典型霍奇金淋巴瘤患者外周血和肿瘤组织中的表达。

Expression of PD-1/PD-L1 in peripheral blood and tumor tissues of patients with classical Hodgkin's lymphoma.

机构信息

Department of Integrated Traditional Chinese and Western Medicine, Public Health Clinical Center of Chengdu, Chengdu, China.

出版信息

Medicine (Baltimore). 2023 Nov 3;102(44):e35757. doi: 10.1097/MD.0000000000035757.

Abstract

Significant biomarkers can predict and estimate the response to chemotherapy for different types of lymphoma. Classical Hodgkin's lymphoma (cHL) and peripheral T-cell lymphoma (PTCL) belong to different types of lymphoma, their prognosis is very different, programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) have been studied in these 2 types of diseases. However, few studies have involved the difference in PD-1/PD-L1 levels between cHL and PTCL. To find out the difference and relevant clinical application value, we collected blood samples of 29 newly diagnosed cHL patients and 11 newly diagnosed PTCL ones. At the same time, tumor tissue paraffin sections of 13 patients with cHL were collected at the initial diagnosis. Flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemical staining were used to detect PD-1/PD-L1 levels in peripheral blood T cells, plasma, and tumor tissues, and the relationship between the above results and clinical data of patients in patients with cHL were investigated. The levels of PD-1 on CD4+ T cells, PD-L1 on CD4+ T cells and PD-1 on CD8+ T cells in peripheral blood of cHL and PTCL patients were higher than those of healthy controls, the level of PD-1 in CD4+ T cells from peripheral blood was higher from cHL patients with stage III-IV (P = .0178), B symptoms (P = .0398), higher lactate dehydrogenase (P = .0056), higher international prognostic index score (P = .0349), and relapsed in later stages (P = .0306). The expression level of soluble PD-L1 (sPD-L1) from cHL (P < .001) and PTCL (P < .0001) patients was higher than that of the healthy control group, and there was higher sPD-L1 level in patients with higher international prognostic index scores (P = .0016). The dynamic detection of sPD-L1 showed that after 2 courses of chemotherapy, the sPD-L1 level in cHL patients with complete remission declined, but the level of sPD-L1 from patients with incomplete remission was not significantly changed (P > .05). In tumor tissues of cHL patients, PD-1(+) was 77%, PD-L1(+) was 69%, PD-1 and PD-L1 expression levels were high. Our results suggest that PD-1 levels in peripheral blood CD4+ T cells are helpful for the stage of disease in patients with cHL, and the dynamic detection of sPD-L1 level is helpful for the judgment of patients with cHL.

摘要

有意义的生物标志物可以预测和评估不同类型淋巴瘤的化疗反应。经典霍奇金淋巴瘤(cHL)和外周 T 细胞淋巴瘤(PTCL)属于不同类型的淋巴瘤,它们的预后差异很大,程序性死亡受体 1(PD-1)及其配体(PD-L1)已在这两种疾病中进行了研究。然而,很少有研究涉及 cHL 和 PTCL 之间 PD-1/PD-L1 水平的差异。为了找出差异和相关的临床应用价值,我们收集了 29 例新诊断的 cHL 患者和 11 例新诊断的 PTCL 患者的血液样本。同时,在初诊时收集了 13 例 cHL 患者的肿瘤组织石蜡切片。采用流式细胞术、酶联免疫吸附试验和免疫组化染色检测外周血 T 细胞、血浆和肿瘤组织中 PD-1/PD-L1 水平,并探讨了上述结果与 cHL 患者临床资料的关系。cHL 和 PTCL 患者外周血 CD4+T 细胞上的 PD-1、CD4+T 细胞上的 PD-L1 和 CD8+T 细胞上的 PD-1 水平均高于健康对照组,来自 III-IV 期(P=0.0178)、B 症状(P=0.0398)、较高的乳酸脱氢酶(P=0.0056)、较高的国际预后指数评分(P=0.0349)和晚期复发(P=0.0306)的 cHL 患者外周血中 CD4+T 细胞上的 PD-1 水平较高。cHL(P<0.001)和 PTCL(P<0.0001)患者可溶性 PD-L1(sPD-L1)的表达水平高于健康对照组,国际预后指数评分较高的患者 sPD-L1 水平较高(P=0.0016)。sPD-L1 的动态检测显示,在 2 个疗程的化疗后,cHL 患者完全缓解时 sPD-L1 水平下降,但不完全缓解患者的 sPD-L1 水平无明显变化(P>0.05)。在 cHL 患者的肿瘤组织中,PD-1(+)为 77%,PD-L1(+)为 69%,PD-1 和 PD-L1 表达水平较高。我们的结果表明,外周血 CD4+T 细胞中的 PD-1 水平有助于 cHL 患者的疾病分期,sPD-L1 水平的动态检测有助于判断 cHL 患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac71/10627677/1cc22932d583/medi-102-e35757-g001.jpg

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