Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer

被引:45
作者
Kim, Hyun-Soo [1 ]
Kim, Ji-Ye [2 ]
Lee, Yong Jae [3 ]
Kim, So Hee [3 ]
Lee, Jung-Yun [3 ]
Nam, Eun Ji [3 ]
Kim, Sunghoon [3 ]
Kim, Sang Wun [3 ]
Kim, Young Tae [3 ]
机构
[1] Yonsei Univ, Coll Med, Severance Hosp, Dept Pathol, Seoul, South Korea
[2] Natl Canc Ctr, Dept Pathol, Goyang, South Korea
[3] Yonsei Univ, Inst Womens Life Med Sci, Dept Obstet & Gynecol, Coll Med, 50-1 Yonsei Ro, Seoul 03722, South Korea
基金
新加坡国家研究基金会;
关键词
Ovarian cancer; High-grade serous ovarian cancer; Neoadjuvant chemotherapy; Programmed cell death ligand 1; Immune checkpoint; Tumor-infiltrating lymphocytes; PD-L1; EXPRESSION; INFILTRATING LYMPHOCYTES; PRIMARY SURGERY; MICROENVIRONMENT; METASTASES;
D O I
10.1016/j.ygyno.2018.08.023
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:414 / 421
页数:8
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