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Research ArticleClinical Studies

Prognostic Value of Tertiary Lymphoid Structures in Epithelial Ovarian Carcinoma

TAKEHIRO NAKAO, KENICHI HARANO, MASASHI WAKABAYASHI, TETSURO TAKI, REIKO WATANABE, HIROSHI TANABE and TORU MUKOHARA
Anticancer Research December 2025, 45 (12) 5543-5555; DOI: https://doi.org/10.21873/anticanres.17889
TAKEHIRO NAKAO
1Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan;
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KENICHI HARANO
1Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan;
2Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan;
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  • For correspondence: kharano{at}east.ncc.go.jp
MASASHI WAKABAYASHI
3Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan;
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TETSURO TAKI
4Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan;
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REIKO WATANABE
4Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan;
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HIROSHI TANABE
5Department of Gynecology, National Cancer Center Hospital East, Kashiwa, Japan
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TORU MUKOHARA
1Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan;
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Abstract

Background/Aim: Tertiary lymphoid structures (TLS) have become the focus of antitumor immunity. However, the prognostic significance of TLS in epithelial ovarian cancer (EOC) treated with primary debulking surgery (PDS) or interval debulking surgery (IDS) remains unclear. Therefore, we aimed to examine TLS in tumor tissues collected during PDS and IDS for patients with EOC to evaluate its prognostic significance.

Patients and Methods: We examined TLS in EOC tumor tissues obtained during PDS or IDS from patients treated between 2017 and 2020 at the National Cancer Center Hospital East, Kashiwa, Japan. The association of tumor-infiltrating lymphocyte frequency, TLS presence, and programmed death-ligand 1 (PD-L1) expression with progression-free (PFS) and overall (OS) survival, and the association between TLS and PD-L1 expression were analyzed.

Results: Overall, 25 specimens (15 from PDS and 10 from IDS) were analyzed. The presence of TLS was associated with a significantly longer OS (median: 32.3 vs. 21.3 months, p=0.0455) in patients who underwent PDS but not in patients who underwent IDS (median: could not be calculated, p=0.9678). No association was identified between TLS and PFS in patients with PDS or with IDS (median: 31.1 vs. 17.3 months, p=0.3970; median: 28.7 vs. 16.3 months for median without TLS, p=0.1653). However, TLS was positively correlated with PD-L1 positivity (p=0.0094).

Conclusion: The prognostic impact of TLS, specifically in pre-chemotherapy specimens, and a positive association between TLS and PD-L1 indicate the potential of TLS as a meaningful biomarker for understanding antitumor immunity and developing immunotherapy for EOC.

Keywords:
  • Ovarian cancer
  • tertiary lymphoid structure
  • tumor microenvironment
  • tumor-infiltrating lymphocytes
  • Received July 25, 2025.
  • Revision received September 17, 2025.
  • Accepted September 26, 2025.
  • Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 45 (12)
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Prognostic Value of Tertiary Lymphoid Structures in Epithelial Ovarian Carcinoma
TAKEHIRO NAKAO, KENICHI HARANO, MASASHI WAKABAYASHI, TETSURO TAKI, REIKO WATANABE, HIROSHI TANABE, TORU MUKOHARA
Anticancer Research Dec 2025, 45 (12) 5543-5555; DOI: 10.21873/anticanres.17889

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Prognostic Value of Tertiary Lymphoid Structures in Epithelial Ovarian Carcinoma
TAKEHIRO NAKAO, KENICHI HARANO, MASASHI WAKABAYASHI, TETSURO TAKI, REIKO WATANABE, HIROSHI TANABE, TORU MUKOHARA
Anticancer Research Dec 2025, 45 (12) 5543-5555; DOI: 10.21873/anticanres.17889
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Keywords

  • ovarian cancer
  • tertiary lymphoid structure
  • Tumor microenvironment
  • tumor-infiltrating lymphocytes
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