Cited by 234Cancer Immunotherapy and BiomarkersCervical Cancer and HPV ResearchT-cell and B-cell Immunology

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Human Leukocyte Antigen Class I, MHC Class I Chain-Related Molecule A, and CD8+/Regulatory T-Cell Ratio: Which Variable Determines Survival of Cervical Cancer Patients?

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Jordanova, Ekaterina S., Gorter, Arko, Ayachi, Ouissam, Prins, Frans, Durrant, Lindy G., Kenter, Gemma G., van der Burg, Sjoerd H., Fleuren, Gert Jan·2008·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-07-4554

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Abstract

Purpose: To investigate the effect of intraepithelial tumor-infiltrating lymphocytes (ieTIL) and their ligands expressed by cervical tumor cells on the outcome of cervical cancer patients. Experimental Design: The prognostic value of ieTILs was investigated in 115 cases of cervical cancer. T-cell subsets, CD57+ cells, and regulatory T cells (Treg) were enumerated. The associations of these different ieTIL subtypes with human leukocyte antigen (HLA) class I and MHC class I chain-related molecule A (MICA) expression were determined in relation to clinical variables and patient survival. Results: Survival analysis showed that a high number of intraepithelial Treg (FoxP3+), a low CD8+/regulatory T-cell ratio, and a weak HLA-A expression were all associated with worse survival (P = 0.034, 0.025, and 0.033, respectively, log-rank test). Further stratification of patient groups based on HLA-A-MICA expression and HLA-A-MICA-CD8+/Treg ratio revealed an even poorer survival (P = 0.005). In a multivariate Cox analysis, low CD8+/Treg ratio (P = 0.047), weak HLA-A-MICA expression (P = 0.003), and weak HLA-A-MICA expression combined with low CD8+/Treg ratio (P = 0.002) were all found to be independent unfavorable prognostic predictors in cervical carcinoma (hazard ratios, 2.7, 4.0, and 4.9, respectively). Conclusion: Weak HLA-A-MICA expression combined with low CD8+/Treg ratio reveals a patient group with the poorest survival in cervical cancer. As a single variable, low CD8+/Treg ratio was a significant independent unfavorable prognostic factor.

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Authors: Jordanova, E. S., Gorter, A., Ayachi, O., Prins, F., Durrant, L. G., Kenter, G. G., van der Burg, S. H., & Fleuren, G. J.
Affiliations: Leiden University Medical Center (NL)
Leiden University (NL)
University of Nottingham (GB)
2Gynecology, and
3Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands and
ORCID: Jordanova, Ekaterina S.
Durrant, Lindy G.
Kenter, Gemma G.
Fleuren, Gert Jan
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2008-04-01
Volume: 14
Issue: 7
Pages: 2028-2035
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-07-4554
OpenAlex: W2127740243
Cited by: 233
References: 44
Citations by year: 2026: 3 · 2025: 11 · 2024: 8 · 2023: 10 · 2022: 15 · 2021: 14 · 2020: 15 · 2019: 17 · 2018: 12 · 2017: 10 · 2016: 12 · 2015: 17 · 2014: 11 · 2013: 11 · 2012: 18
FWCI: 8.62
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: cervical cancer, tumor-infiltrating lymphocytes, regulatory T cells, CD8/Treg ratio, HLA-A, mica, prognostic factors, patient survival, Foxp3, CD57, tumor immune microenvironment
MeSH terms: Adult, Aged, Aged, 80 and over, Uterine Cervical Neoplasms, Female, Fluorescent Antibody Technique, Humans, Middle Aged, Prognosis, Biomarkers, Tumor, HLA-A Antigens, Histocompatibility Antigens Class I, Polymerase Chain Reaction, Lymphocytes, Tumor-Infiltrating, CD8-Positive T-Lymphocytes, T-Lymphocytes, Regulatory, Kaplan-Meier Estimate

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Human Leukocyte Antigen Class I, MHC Class I Chain-Related Molecule A, and CD8+/Regulatory T-Cell Ratio: Which Variable Determines Survival of Cervical Cancer Patients?

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