RT Journal Article SR Electronic T1 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? JF Clinical Cancer Research JO Clin Cancer Res FD American Association for Cancer Research SP 2028 OP 2035 DO 10.1158/1078-0432.CCR-07-4554 VO 14 IS 7 A1 Jordanova, Ekaterina S. A1 Gorter, Arko A1 Ayachi, Ouissam A1 Prins, Frans A1 Durrant, Lindy G. A1 Kenter, Gemma G. A1 van der Burg, Sjoerd H. A1 Fleuren, Gert Jan YR 2008 UL http://clincancerres.aacrjournals.org/content/14/7/2028.abstract AB 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.