PT  - JOURNAL ARTICLE
AU  - Jordanova, Ekaterina S.
AU  - Gorter, Arko
AU  - Ayachi, Ouissam
AU  - Prins, Frans
AU  - Durrant, Lindy G.
AU  - Kenter, Gemma G.
AU  - van der Burg, Sjoerd H.
AU  - Fleuren, Gert Jan
TI  - Human Leukocyte Antigen Class I, MHC Class I Chain-Related Molecule A, and CD8<sup>+</sup>/Regulatory T-Cell Ratio: Which Variable Determines Survival of Cervical Cancer Patients?
AID  - 10.1158/1078-0432.CCR-07-4554
DP  - 2008 Apr 01
TA  - Clinical Cancer Research
PG  - 2028--2035
VI  - 14
IP  - 7
4099  - http://clincancerres.aacrjournals.org/content/14/7/2028.short
4100  - http://clincancerres.aacrjournals.org/content/14/7/2028.full
SO  - Clin Cancer Res2008 Apr 01; 14
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.