Programmed death-1 ligands PD-L1 and PD-L2 show distinctive and restricted patterns of expression in lymphoma subtypes
Programmed death-1 ligands PD-L1 and PD-L2 show distinctive and restricted patterns of expression in lymphoma subtypes
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DOI：
10.1016/j.humpath.2017.10.029
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发表时间：
2018-01-01
期刊：
影响因子：
3.3
通讯作者：
Zhao, Shuchun
中科院分区：
文献类型：
--
作者：
Panjwani, Poonam K.;Charu, Vivek;Zhao, Shuchun
在实体瘤和复发性/难治性经典霍奇金淋巴瘤和慢性淋巴细胞白血病中使用免疫检查点阻断的免疫疗法的成功为血液恶性肿瘤的靶向治疗带来了希望。由于免疫调节治疗的疗效与表达程序性死亡（PD-1）配体的细胞数量相关，我们使用免疫组织化学方法在超过702例诊断性淋巴瘤活检中评估了PD-L1和PD-L2蛋白的表达。在经典霍奇金淋巴瘤中，PD-L1和PD-L2分别在82%和41%的病例中表达，PD-L1而不是PD-L2表达与肿瘤细胞中的EB病毒相关。PD-L1在80%的间变性大细胞淋巴瘤、血管免疫母细胞性T细胞淋巴瘤和滤泡树突状细胞肉瘤中检测到; 75%的结节性淋巴细胞为主型霍奇金淋巴瘤; 53%的原发性纵隔大B细胞淋巴瘤; 39%的结节性NIUT细胞淋巴瘤; 26%的外周T细胞淋巴瘤; 10%的弥漫性大B细胞淋巴瘤;以及非常罕见的外套膜、边缘区和小淋巴细胞性淋巴瘤。PD-L2染色存在于78%的原发性纵隔大B细胞淋巴瘤中，但在所有其他类别中的病例较少，包括40%的滤泡树突状细胞肉瘤和7%的间变性大细胞淋巴瘤。我们的结果证实并扩展了先前对PD-L1的研究，并提供了淋巴瘤中PD-L2表达的新数据。在某些肿瘤类型中的差异表达模式以及在PD-L1缺失的情况下PD-L2的表达提高了对淋巴瘤患者的其他亚群进行靶向治疗的可能性。(C)2017爱思唯尔公司All rights reserved.
The success of immunotherapy using immune checkpoint blockade in solid tumors and in relapsed/refractory classical Hodgkin lymphoma and chronic lymphocytic leukemia holds promise for targeted therapy in hematologic malignancies. Because efficacy of immunomodulatory therapy is correlated with numbers of cells that express programmed death (PD-1) ligands, we evaluated the expression of PD-L1 and PD-L2 proteins using immunohistochemistry in more than 702 diagnostic lymphoma biopsies. In classical Hodgkin lymphoma, PD-L1 and PD-L2 were expressed in 82% and 41% of cases, respectively, and PD-L1 but not PD-L2 expression correlated with Epstein-Barr virus in tumor cells. PD-L1 staining was detected in 80% of anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, and follicular dendritic cell sarcoma; 75% of nodular lymphocyte predominant Hodgkin lymphoma; 53% of primary mediastinal large B-cell lymphoma; 39% of extranodal NIUT cell lymphoma; 26% of peripheral T-cell lymphoma; 10% of diffuse large B-cell lymphoma; and very rare examples of mantle, marginal zone, and small lymphocytic lymphomas. PD-L2 staining was present in 78% of primary mediastinal large B-cell lymphoma but in fewer cases in all other categories including 40% of follicular dendritic cell sarcoma and 7% of anaplastic large cell lymphoma. Our results confirm and extend prior studies of PD-L1 and provide new data of PD-L2 expression in lymphomas. The differential expression pattems in some tumor types and the expression of PD-L2 in the absence of PD-L1 raise the possibility of targeted therapy for additional subsets of patients with lymphoma. (C) 2017 Elsevier Inc. All rights reserved.