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Anti-PD-1 Treatment Restores Effector Function in Exhausted-like T Cells from Malignant Ascites of Ovarian Cancer Patients

delete2026-08-13
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OA
AI
D
Diana Luísa Almeida-Nunes
A
Ana Mendes‐Frias
M
Mariana Nunes
V
Verónica Ferreira
C
Cláudia Lobo
P
Paula Monteiro
M
Miguel Henriques Abreu
C
Carla Bartosch
C
Cláudia Nóbrega
R
Ricardo Jorge Dinis‐Oliveira *
R
Ricardo Silvestre *
S
Sara Ricardo
DOI:10.3390/cancers18162612delete
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Abstract

Abstract

En 中文
Background/Objectives: High-grade serous carcinoma (HGSC) represents the most frequent subtype of epithelial ovarian cancer (OC) and is associated with malignant ascitic fluid (MAF), which fosters a pro-inflammatory microenvironment that supports tumor progression. Given its rich cellular and soluble content, MAF offers a valuable window into tumor–host interactions and disease dynamics. This study examines the immune landscape of MAF samples from 22 newly diagnosed treatment-naïve HGSC patients. Methods: Immune cell phenotypes and cytokine profiles were analyzed via flow cytometry. Patients were stratified according to time to death or recurrence (TDR), using a six-month interval from diagnosis to either documented recurrence or disease-specific death as the cutoff: TDR < 6 months defined as the worse prognosis group, whereas TDR ≥ 6 months defined the better prognosis group. The expression of immune checkpoint molecules on T cells and the effects of PD-1 blockade with Pembrolizumab were also assessed. Results: Patients with worst prognosis exhibited a marked pro-inflammatory cytokine milieu, with elevated levels of TNFα, IL-1β, IL-23, and IFNγ. Concurrently, their CD4+ and CD8+ T cells displayed evidence of a functional exhaustion-associated phenotype, marked by heightened expression of the inhibitory receptors TIM-3, PD-1, and LAG-3. Notably, treatment with Pembrolizumab (a PD-1 checkpoint inhibitor) significantly enhance T cell effector function. Conclusions: These results underscore a potential immunotherapeutic approach in anti-tumor immunity among selected HGSC patients, presenting a compelling direction for advancing OC treatment.
Keywords:
high-grade serous carcinoma
malignant ascitic fluid
tumor immune microenvironment
anti-PD-1
T cell exhaustion-like phenotype

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Cancers cover
Cancers
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4.4
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6.3K
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P
portuguese oncology institute of porto
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60
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U
University Institute of Health Sciences Cespu
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U
University of Porto
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university of minho
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