Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer
Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer
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DOI：
10.1016/j.ygyno.2018.08.023
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发表时间：
2018-12-01
影响因子：
4.7
通讯作者：
Kim, Young Tae
中科院分区：
文献类型：
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作者：
Kim, Hyun-Soo;Kim, Ji-Ye;Kim, Young Tae
目标。目的探讨晚期高级别浆液性卵巢癌(HGSOC)新辅助化疗(NAC)后残留肿瘤组织中程序性细胞死亡配体1(PD-L1)和免疫检查点标志物的表达与预后的关系。我们收集了2006至2017年间晚期HGSOC患者NAC治疗前和治疗后的肿瘤样本。对131例NAC术后肿瘤组织标本进行免疫组织化学染色。免疫组织化学染色检测PD-L1和免疫检查点标志物的表达，并检测肿瘤浸润性淋巴细胞(TIL)的状态。我们检查了蛋白表达状态和患者预后之间是否存在显著的相关性，以及蛋白表达水平是否因NAC.Results的反应而发生显著变化。检测了113例患者肿瘤细胞中PD-L1的表达，其中12例(10.6%)在NAC后组织中高表达(-gt；_25%)。然而，这些高水平与无进展生存期(PFS；P=0.348)或总生存期(OS；P=0.699)无关。同样，在评估的107名患者中，高间质TIL[>；=50%；n=16(15.0%)]对PFS(P=0.250)或OS(P=0.800)没有任何显著影响。此外，残留肿瘤中大量的TIL(上皮内、CD8+和Foxp3+)和免疫检查点标志物(PD-1、ICOS和LAG-3)的表达并没有带来任何显著的生存益处。NAC对PD-LT表达和间质TIL的影响在不同患者之间有很大差异。尽管PD-L1和免疫检查点标记物在NAC后残留肿瘤中的表达对HGSOC患者的预后没有影响，但NAC后对化疗耐药肿瘤中这些蛋白的评估可能有助于选择患者进行免疫治疗试验。(C)2018 Elsevier Inc.保留所有权利。
Objective. To investigate the prognostic value of the expressions of programmed cell death ligand 1 (PD-L1) and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy (NAC) for advanced high-grade serous ovarian cancer (HGSOC).Methods. We collected pre- and post-NAC tumor samples from patients with advanced HGSOC between 2006 and 2017. Post-NAC tumor tissue samples were available for immunostaining from 131 patients. The expressions of PD-L1 and immune checkpoint markers were assessed by immunohistochemical staining and the status of tumor-infiltrating lymphocytes (TILs) was also evaluated. We examined whether there are significant associations between protein expression status and patient outcomes and whether significant changes in protein expression levels occurred in response to NAC.Results. PD-L1 expression in the tumor cells was evaluated in 113 patients, 12 (10.6%) of whom had high PDL1 expression (>_25%) in post-NAC tissues. However, these high levels were not associated with progression-free survival (PFS; P = 0.348) or overall survival (OS; P = 0.699). Similarly, high stromal TILs [>= 50%; n = 16 (15.0%)] among the 107 patients evaluated did not show any significant impact on PFS (P = 0.250) or OS (P = 0.800). Moreover, an abundance of TILs (intraepithelial, CD8+, and Foxp3+ ) and the expression of immune checkpoint markers (PD-1, ICOS, and LAG-3) in residual tumors did not confer any significant survival benefit. The impact of NAC on PD-Lt expression and stromal TILs varied considerably among individual patients.Conclusion. Although the expression of PD-L1 and immune checkpoint markers in residual tumors after NAC had no prognostic impact on survival in patients with HGSOC, post-NAC evaluation of these proteins in chemoresistant tumors may help select patients for immunotherapy trials. (C) 2018 Elsevier Inc. All rights reserved.