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Comprehensive Immunohistochemical Study of Programmed Cell Death Ligand 1 (PD-L1): Analysis in 5536 Cases Revealed Consistent Expression in Trophoblastic Tumors.

5536例免疫组化综合分析表明滋养层肿瘤一致表达程序性细胞死亡配体1(PD-L1)

Inaguma S,Wang Z,Lasota J,Sarlomo-Rikala M,McCue PA,Ikeda H,Miettinen M

Abstract

Programmed cell death 1/programmed cell death ligand (PD-1/PD-Ls) axis is crucial for the modulation of immune responses and self-tolerance. Also, aberrant PD-L1 expression on the tumor cells or tumor-associated inflammatory cells accelerates immune evasion of tumor cells. In the past decade, PD-1/PD-L immune checkpoint inhibitors were introduced to cancer treatment trials and, in some cases, showed significant anticancer effects. PD-L1 immunohistochemical staining is considered a potential predictor of clinical response to PD-1/PD-L immune checkpoint inhibitor treatment. However, immunohistochemical data on PD-L1 expression in different types of cancer especially rare entities remain incomplete. In this study, PD-L1 expression was immunohistochemically analyzed in 5536 tumors including germ cell, epithelial, mesenchymal, melanocytic/neuroectodermal, and lymphohematopoietic tumors, as well as in a set of human normal tissues including a fetus. Immunohistochemical analysis was performed with E1L3N rabbit monoclonal antibody and Leica Bond Max automation using multitumor blocks containing up to 70 tumor samples. PD-L1 was constitutively and strongly expressed in placental trophoblasts as well as choriocarcinomas and trophoblastic components of germ cell tumors. Also, the neoplastic cells of classical Hodgkin lymphoma, anaplastic large cell lymphoma, schwannoma, thymoma, and squamous cell carcinoma of various sites frequently expressed PD-L1. In gastrointestinal adenocarcinomas, PD-L1-expression was associated with EBER positivity and mismatch-repair deficiency. In addition, PD-L1 was variably expressed in non-neoplastic macrophages and dendritic cells. PD-L1 immunohistochemistry may have some role in the immunophenotypic differential diagnosis of tumors and pinpointing potential candidates for anti-PD-1/PD-L immune checkpoint therapy.

摘要

程序性细胞死亡1/程序性细胞死亡配体(PD-1/PD-Ls)轴对免疫反应调节和自身耐受性至关重要。肿瘤细胞或肿瘤相关炎症细胞异常表达PD-L1,加速肿瘤细胞免疫逃逸。过去十年,PD-1/PD-L免疫检查点抑制剂引入癌症治疗试验,一些病例显示处显著抗癌效应。PD-L免疫组化染色被认为是PD-1/PD-L免疫检查点抑制剂治疗临床有效的潜在预测指征。但PD-L1在不同类型癌、特别是罕见疾病中表达的免疫组化数据仍不完善。

本研究分析5536例肿瘤中PD-L1的免疫组化表达,包括生殖细胞、上皮、间叶、黑色素细胞/神经外胚层和淋巴造血肿瘤,以及包括一例胎儿在内的一组人正常组织。免疫组化分析运用E1L3N兔单克隆抗体和Leica Bond Max自动染色机,使用多肿瘤组织块,包含高达70个肿瘤样本。胎盘滋养层和绒毛膜癌及生殖细胞肿瘤中的滋养层成份一致性强表达PD-L1。经典型霍奇金淋巴瘤、间变性大细胞淋巴瘤、神经鞘瘤、胸腺瘤和不同部位鳞癌的肿瘤性细胞常表达PD-L1。胃肠道腺癌中,PD-L1表达与EBER阳性和错配修复缺陷相关。另外,PD-L1程度不一的表达于非肿瘤性巨噬细胞和树突细胞。PD-L1免疫组化可能在肿瘤免疫表型鉴别诊断、精确筛选抗PD-1/PD-L免疫检查点治疗方面有一些作用。

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