PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies.
PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies.
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DOI：
10.1158/1078-0432.ccr-13-0855
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Rodig SJ
中科院分区：
文献类型：
--
作者：
Chen BJ;Chapuy B;Ouyang J;Sun HH;Roemer MG;Xu ML;Yu H;Fletcher CD;Freeman GJ;Shipp MA;Rodig SJ
程序性死亡配体1(PD-L1)是一种免疫调节分子，由抗原提呈细胞和选择性肿瘤细胞与T细胞上的受体结合来抑制T细胞免疫。针对PD-1/PD-L1途径的免疫疗法在实体瘤患者中显示出持久的抗肿瘤效果。PD-L1可由含有经典霍奇金淋巴瘤(CHL)的Reed-Sternberg细胞和含有EBV阳性的移植后淋巴增生性疾病(PTLDs)的恶性B细胞表达。我们试图确定PD-L1的表达是否代表侵袭性B细胞淋巴瘤和病毒和免疫缺陷相关肿瘤免疫逃避的一般策略。使用新型抗体和福尔马林固定石蜡包埋(FFPE)组织活检，我们检测了237例原发肿瘤PD-L1蛋白的表达。PD-L1蛋白在结节性硬化性CHL、混合细胞性CHL、原发性纵隔大B细胞淋巴瘤、富含T细胞/组织细胞的B细胞淋巴瘤、EBV阳性和阴性PTLD、EBV相关弥漫性大B细胞淋巴瘤(DLBCL)、浆母细胞淋巴瘤、结外NK/T细胞淋巴瘤、鼻咽癌和HHV8相关的原发渗出性淋巴瘤中均有较强的表达。在这些肿瘤中，PD-L1在恶性肿瘤细胞和肿瘤浸润性巨噬细胞中高表达。相反，恶性和非恶性细胞都不表达可检测到的PD-L1，包括结节状淋巴细胞为主的霍奇金淋巴瘤、非特指的DLBCL、Burkitt淋巴瘤和HHV8相关的Kaposi肉瘤。某些侵袭性B细胞淋巴瘤和与无效T细胞免疫反应相关的病毒和免疫缺陷相关的恶性肿瘤在肿瘤细胞和浸润性巨噬细胞上表达PD-L1。这些结果确定了PD-1/PD-L1导向治疗应考虑的一组肿瘤，并验证了在FFPE组织活检中检测PD-L1的方法。
Programmed death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engage receptors on T cells to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable anti-tumor effects in a subset of patients with solid tumors. PD-L1 can be expressed by Reed-Sternberg cells comprising classical Hodgkin lymphoma (CHLs) and by malignant B cells comprising EBV-positive post-transplant lymphoproliferative disorders (PTLDs). We sought to determine whether the expression of PD-L1 represents a general strategy of immune evasion among aggressive B-cell lymphomas and virus- and immunodeficiency-associated tumors. Using novel antibodies and formalin-fixed, paraffin-embedded (FFPE) tissue biopsies, we examined 237 primary tumors for expression of PD-L1 protein. Robust PD-L1 protein expression was found in the majority of nodular sclerosis CHL, mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the non-malignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1. Certain aggressive B-cell lymphomas and virus- and immunodeficiency-associated malignancies associated with an ineffective T-cell immune response express PD-L1 on tumor cells and infiltrating macrophages. These results identify a group of neoplasms that should be considered for PD-1/PD-L1-directed therapies, and validate a method to detect PD-L1 in FFPE tissue biopsies.