Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome
Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome
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DOI：
10.1007/s11060-017-2451-7
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发表时间：
2017-06-01
影响因子：
3.9
通讯作者：
Matsumura, Akira
中科院分区：
文献类型：
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作者：
Miyazaki, Tsubasa;Ishikawa, Eiichi;Matsumura, Akira
胶质母细胞瘤（GBM）是最常见的恶性脑肿瘤类型，预后极差。尽管进行了积极的治疗，但大多数患者在12个月内复发，复发后的患者结局非常糟糕。本研究旨在阐明初次和二次切除肿瘤标本中分子表达的变化，包括程序性细胞死亡1（PD-1）和PD-配体1（PD-L1），并探讨这些表达对胶质母细胞瘤二次手术后患者结局的影响。我们调查了16例年龄在14岁至65岁之间的患者，他们患有组织学证实的WHO IV级GBM，其原发肿瘤在2008年至2014年期间切除，并接受了分次放疗和替莫唑胺治疗。入组了4例使用自体福尔马林固定肿瘤疫苗进行免疫治疗的患者。所有患者均在24个月内肿瘤复发后接受二次切除。我们使用一组免疫系统分子标记物对患者的初次和二次切除肿瘤进行免疫组织化学检查，并评估标记物表达是否与临床结果相关。与初次切除标本相比，二次切除标本中肿瘤浸润淋巴细胞上的CD 3、CD 8和PD-1显著增加（p aEuroe0.05）。所有患者在初次和二次切除标本中的肿瘤细胞上均表达PD-L1。根据初次或二次切除标本上PD-1的中位IHC评分将患者分为高表达组和低表达组。在最初切除标本的高PD-1或PD-L1组和低PD-1或PD-L1组之间未观察到患者结局的显著差异。在二次切除标本高表达组中，大部分患者评分较初次切除标本有所提高。二次切除标本PD-1高表达评分组与无进展生存期长、复发后生存期短相关。在几乎所有初始和继发标本中均检测到PD-L1表达。二次标本PD-1高表达的患者二次切除后预后差。PD-1/PD-L1通路可能与胶质母细胞瘤二次手术后的患者结局相关。
Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma. We investigated 16 patients, ranging in age from 14 to 65 years, with histologically verified WHO grade IV GBM, whose original tumor was resected between 2008 and 2014, and treated with fractionated radiotherapy and temozolomide. Four patients who were treated with immunotherapy using autologous formalin-fixed tumor vaccine were enrolled. All of the patients underwent secondary resection after tumor recurrence within 24 months. We carried out an immunohistochemical examination of the initial and secondary resected tumors from patients using a panel of immune system molecular markers, and assessed whether marker expression correlated with clinical outcomes. CD3, CD8 and PD-1 on tumor-infiltrating lymphocytes was significantly increased in secondary resected specimens compared with initially resected specimens (p aEuroe0.05). All patients expressed PD-L1 on tumor cells in initial and secondary resection specimens. Patients were divided into high or low expression group by median IHC score of PD-1 on initial or secondary resected specimens. No significant differences in patient outcomes were observed between high and low PD-1 or PD-L1 groups of initially resected specimens. In high expression group of secondary resected specimens, most patients score had increased which compared with initial resected tumor specimens. The PD-1 high expression score group of secondary resected specimens was associated with long progression-free survival and short survival after recurrence. PD-L1 expression was detected in almost all initial and secondary specimens. Patients with high PD-1 expression of secondary specimen had bad prognosis after secondary resection. PD-1/PD-L1 pathway may be associated with patient outcome after second surgery of glioblastoma.