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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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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The number and functional orientation of tumor-infiltrating CD4+ and CD8+ T cells and the presence of M1 type macrophages strongly correlate with survival in patients with cervical cancer after CRT.
“Previous studies have reported that the number and functional orientation of tumor-infiltrating CD4+ and CD8+ T cells and the presence of M1 type macrophages strongly correlates with survival in patients with CC after CRT23,24.”
From Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation (2021) · cites this paper as [24]
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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
- Venue
- Clinical Cancer Research
- Published
- 2008-04-01
- Volume
- 14
- Issue
- 7
- Pages
- 2028-2035
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- 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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