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Association of Tumor-Infiltrating Lymphocytes and Inflammation Status with Survival Outcome in Patients with High-Grade Serous Ovarian Carcinoma

  • Simona Miceska
  • , Cvetka Grašič Kuhar
  • , Snježana Frković Grazio
  • , Erik Škof
  • , Praveen Krishnamoorthy
  • , Dineo Khabele
  • , Veronika Kloboves Prevodnik

Research output: Contribution to journal › Article › peer-review

Abstract

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) and inflammation status are emerging prognostic markers in various cancers, but their significance in high-grade serous ovarian carcinoma (HGSC) remains unclear. Our objective was to evaluate different TIL subtypes and inflammation status in relation to progression-free survival (PFS) in primary HGSC. Methods: CD3+/CD4+/CD8+/PD-1+ stromal TILs (sTILs) and intraepithelial TILs (iTILs) were evaluated by manual assessment and digital image analysis (DIA), following TIL Working Group recommendations. Inflammation status was evaluated through the following scores: systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), CA125, and lactate dehydrogenase (LDH). Results: CD8+ TILs were the most prevalent subtype in both iTILs and sTILs. However, sTILs were significantly more abundant than iTILs (p < 0.001) among all subsets, except for PD-1+ cells. DIA results of TIL assessments were in agreement with manual assessments. High stromal CD3+ and CD8+ TILs, PIV, CA125, and LDH, were associated with improved PFS. Potential independent prognostic factors for PFS in manual assessment were PIV (HR = 0.32, CI 95% = 0.12–0.82) and CD8+ sTILs (HR = 0.30, CI 95% = 0.12–0.79), whereas in DIA assessment they were CD3+ sTILs (HR = 0.31, CI 95% = 0.15–0.67), PIV (HR = 0.35, 95% CI 0.13–0.96), and residual disease (HR = 0.21 95% CI 0.08–0.53). Conclusions: CD3+/CD8+ sTILs and PIV are promising prognostic indicators in HGSC; however, further research is needed to confirm their clinical utility.

Original languageEnglish
Article number2269
JournalCancers
Volume17
Issue number14
DOIs
StatePublished - Jul 2025

Keywords

  • digital-image analysis
  • high-grade serous ovarian carcinoma
  • immunohistochemistry
  • inflammation status
  • manual scoring
  • prognostic biomarkers
  • tumor-infiltrating lymphocytes

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