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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)414-421
Number of pages8
JournalGynecologic Oncology
Volume151
Issue number3
DOIs
Publication statusPublished - 2018 Dec

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Residual Neoplasm
Ovarian Neoplasms
Cell Death
Biomarkers
Ligands
Tumor-Infiltrating Lymphocytes
Drug Therapy
Survival
Neoplasms
Proteins
Immunotherapy
Disease-Free Survival
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynaecology

Cite this

Kim, Hyun Soo ; Kim, Ji Ye ; Lee, Yong Jae ; Kim, So Hee ; Lee, Jung Yun ; Nam, Eun Ji ; Kim, Sunghoon ; Kim, Sang Wun ; Kim, Young Tae. / Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer. In: Gynecologic Oncology. 2018 ; Vol. 151, No. 3. pp. 414-421.
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title = "Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer",
abstract = "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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Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer. / Kim, Hyun Soo; Kim, Ji Ye; Lee, Yong Jae; Kim, So Hee; Lee, Jung Yun; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae.

In: Gynecologic Oncology, Vol. 151, No. 3, 12.2018, p. 414-421.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer

AU - Kim, Hyun Soo

AU - Kim, Ji Ye

AU - Lee, Yong Jae

AU - Kim, So Hee

AU - Lee, Jung Yun

AU - Nam, Eun Ji

AU - Kim, Sunghoon

AU - Kim, Sang Wun

AU - Kim, Young Tae

PY - 2018/12

Y1 - 2018/12

N2 - 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.

AB - 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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