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

 Hyun-Soo Kim  ;  Ji-Ye Kim  ;  Yong Jae Lee  ;  So Hee Kim  ;  Jung-Yun Lee  ;  Eun Ji Nam  ;  Sunghoon Kim  ;  Sang Wun Kim  ;  Young Tae Kim 
 GYNECOLOGIC ONCOLOGY, Vol.151(3) : 414-421, 2018 
Journal Title
Issue Date
Adult ; Aged ; B7-H1 Antigen/metabolism* ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology* ; Middle Aged ; Neoadjuvant Therapy/methods* ; Ovarian Neoplasms/drug therapy* ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Retrospective Studies
High-grade serous ovarian cancer ; Immune checkpoint ; Neoadjuvant chemotherapy ; Ovarian cancer ; Programmed cell death ligand 1 ; Tumor-infiltrating lymphocytes
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 PD-L1 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-L1 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.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Wun(김상운) ORCID logo https://orcid.org/0000-0002-8342-8701
Kim, Sung Hoon(김성훈) ORCID logo https://orcid.org/0000-0002-1645-7473
Kim, Young Tae(김영태) ORCID logo https://orcid.org/0000-0002-7347-1052
Kim, Hyun-Soo(김현수)
Nam, Eun Ji(남은지) ORCID logo https://orcid.org/0000-0003-0189-3560
Lee, Yong Jae(이용재) ORCID logo https://orcid.org/0000-0003-0297-3116
Lee, Jung-Yun(이정윤) ORCID logo https://orcid.org/0000-0001-7948-1350
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