ArticleProceedings of the National Academy of Sciences of the United States of America2005
Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1,391 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase II Open Label Nonrandomized Trial of the Anti PD 1 Therapy Pembrolizumab With First Line Platinum Based Chemotherapy Followed by 12 Months Pembrolizumab Monotherapy for Patients With Stage III/IV Epithelial Ovarian Cancer
Phenotypic Characterization Tumor-infiltrating Lymphocytes at Diagnosis and After Chemotherapy in Advanced High-grade Serous Ovarian Cancer in Blood, Ascites, Peritoneal Biopsy
Who cites it
1,391 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial.Nature medicine · 2025Trial
- A clinical study of tremelimumab, alone or in combination with olaparib, for recurrent epithelial ovarian cancer.Gynecologic oncology · 2025Trial
- Integrative multi-omics analysis uncovers tumor-immune-gut axis influencing immunotherapy outcomes in ovarian cancer.Nature communications · 2024Trial
- Phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer: primary analysis in the original cohort of KGOG3046/TRU-D.Journal for immunotherapy of cancer · 2023Trial
- Trial
- Profiling tumor immune microenvironment of epithelial ovarian carcinoma.Oncoimmunology · 2026Article
- Personalized neoantigen-targeting cancer vaccines in ovarian cancer: a phase 1 trial.Nature medicine · 2026Article
- Standardized Upstream Processing of Ovarian Cancer Surgical Specimens for TIL-Oriented Cellular Workflows.Cancers · 2026Article
- Immunotherapy in Gynecologic Cancers: Current Evidence, Biomarker-Driven Practice, and Future Directions.Cancers · 2026Review
- Immunological and prognostic impact of NRF2 in high grade serous ovarian cancer.Genes and immunity · 2026Article
- Review
- Prognostic Value of Morphological Characteristics and Immune Microenvironment in High-Grade Serous Cancer (HGSC).Cancers · 2026Article
- Transcriptomic analysis of tissue-resident memory T cells of the fallopian tube reveals a precursor immune surveillance network for ovarian cancer prevention.Nature communications · 2026Article
- Recurrence-free survival is prolonged in high-grade serous ovarian cancer with high PD-L1 expression.BMC cancer · 2026Article
- CTLA-4 Blockade Combined with PD-1/PD-L1 Inhibition Enhances Cytokine Production and T-Cell Activation in Ex Vivo Ovarian Cancer Cultures.International journal of molecular sciences · 2026Article
- CpG 1018 augments mRNA vaccine-induced anti-tumor immunity by potentiating CD8+ T cell responses.Molecular therapy. Oncology · 2026Article
- Lactate Uptake by MCT4 Facilitates Stability and Suppressive Function of Tumor-Infiltrating Regulatory T Cells by Promoting Foxp3 Lactylation.International journal of molecular sciences · 2026Article
- Extrauterine mesonephric-like carcinoma: a tumor with a cold lymphocytic immune microenvironment.Virchows Archiv : an international journal of pathology · 2026Article
- Association of CXCR7 and CXCR4 expression with tumor immune phenotypes in tubo-ovarian high-grade serous carcinoma.Irish journal of medical science · 2026Article
1,331 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In a recent report, [Zhang et al. (2003) N. Engl. J. Med. 348, 203-213], the presence of CD3+ tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. We performed immunohistochemical analysis for TILs and cancer testis antigens in 117 cases of epithelial ovarian cancer. The interrelationship between subpopulations of TILs and expression of cancer testis antigens was investigated, as well as between TILs and overall survival. The median follow-up of the patients was 31 months. Patients with higher frequencies of intraepithelial CD8+ T cells demonstrated improved survival compared with patients with lower frequencies [median = 55 versus 26 months; hazard ratio = 0.33; confidence interval (C.I.) = 0.18-0.60; P = 0.0003]. No association was found for CD3+ TILs or other subtypes of intraepithelial or stromal TILs. However, the subgroups with high versus low intraepithelial CD8+/CD4+ TIL ratios had median survival of 74 and 25 months, respectively (hazard ratio = 0.30; C.I. = 0.16-0.55; P = 0.0001). These results indicate that CD4+ TILs influence the beneficial effects of CD8+ TIL. This unfavorable effect of CD4+ T cells on prognosis was found to be due to CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Treg; suppressor T cells), as indicated by survival of patients with high versus low CD8+/Treg ratios (median = 58 versus 23 months; hazard ratio = 0.31; C.I. = 0.17-0.58; P = 0.0002). The favorable prognostic effect of intraepithelial CD8+ TILs did not correlate with concurrent expression of NY-ESO-1 or MAGE antigens. We conclude that intraepithelial CD8+ TILs and a high CD8+/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer.
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