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首页> 外文期刊>Histopathology: Official Journal of the British Division of the International Academy of Pathology >Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in post-transplant lymphoproliferative disorders: association with Epstein-Barr virus, PD-L1 copy number alterations, and outcome
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Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in post-transplant lymphoproliferative disorders: association with Epstein-Barr virus, PD-L1 copy number alterations, and outcome

机译：后移植后淋巴抑制性疾病中的编程细胞死亡1（PD1）/编程的细胞死亡配体1（PD-L1）轴的临床病理评价：与Epstein-Barr病毒相关联，PD-L1拷贝数改变和结果

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Aims The clinical implications of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in patients with post-transplant lymphoproliferative disorders are largely unknown, and its association with Epstein-Barr virus (EBV) status and PD-L1 copy number alterations (CNAs) has not been thoroughly studied. Methods and results PD1/PD-L1 expression was studied in 50 adult post-transplant lymphoproliferative disorders, and the correlations with PD-L1 CNAs, EBV, clinicopathological features and outcome were evaluated. Thirty-seven (74%) cases were classified as diffuse large B-cell lymphoma (DLBCL), nine (18%) cases were classified as polymorphic, and four (8%) cases were classified as classic Hodgkin lymphoma. Thirty-four cases were EBV-positive, with 29 of 34 (85%) having latency II or III, and 15 of 34 (44%) having viral replication. PD-L1 expression in tumour cells and tumour-associated macrophages was observed in 30 (60%) and 37 (74%) cases, respectively. PD1 positivity was seen in 16 (32%) cases. PD-L1 expression was associated with EBV with latency II or III (P = 0.001) and organ rejection (P = 0.04), and, in DLBCL, with non-germinal centre type DLBCL (P < 0.001). Cases with PD-L1-positive tumour cells showed a higher number of PD-L1 CNAs than PD-L1-negative cases (P = 0.001). Patients with EBV/latency III/replication and simultaneous PD-L1 expression showed the worst overall survival (P < 0.001). Conclusions The PD1/PD-L1 axis is deregulated in post-transplant lymphoproliferative disorders, with frequent PD-L1 expression and PD1 negativity. PD-L1 expression is associated with EBV latency II or III and PD-L1 CNAs, and probably reflects a proinflammatory tumour microenvironment. The combined analysis of EBV status and PD-L1 expression may help to identify deeply immunosuppressed patients who can benefit from immune reconstitution approaches.
机译：旨在将编程的细胞死亡1（PD1）/编程的细胞死亡 - 配体1（PD-L1）轴在移植后淋巴抑制性疾病患者中的临床意义主要是未知的，其与Epstein-Barr病毒（EBV）状态的关系并且PD-L1拷贝数改变（CNA）尚未彻底研究。方法和结果在50个成年后淋巴抑制性疾病中研究了PD1 / PD-L1表达，评价了与PD-L1 CNA，EBV，临床病理特征和结果的相关性。将三十七（74％）病例分类为弥漫性大B细胞淋巴瘤（DLBCL），九（18％）病例被归类为多晶型，四（8％）病例分类为经典霍奇金淋巴瘤。 34例均为EBV阳性，具有29个（共34个（85％），具有潜伏期II或III，15个具有病毒复制的15个（44％）。在30（60％）和37例（74％）病例中观察到肿瘤细胞和肿瘤相关巨噬细胞中的PD-L1表达。在16例（32％）病例中可以看到PD1阳性。 PD-L1表达与eBV有潜水II或III（P = 0.001）和器官排斥（P = 0.04），并且在DLBCL中，具有非生发中心型DLBCL（P <0.001）。具有PD-L1阳性肿瘤细胞的病例显示比PD-L1阴性病例更多的PD-L1 CNA（P = 0.001）。患有EBV /潜伏期III /复制和同时PD-L1表达的患者显示出最糟糕的总存活率（P <0.001）。结论PD1 / PD-L1轴在移植后淋巴抑制性疾病中解毒，具有频繁的PD-L1表达和PD1消极性。 PD-L1表达与EBV等待时间II或III和PD-L1 CNA相关，并且可能反映促炎肿瘤微环境。 EBV状态和PD-L1表达的综合分析可能有助于鉴定可以从免疫重建方法中受益的深度免疫抑制患者。

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