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.
- cervical cancer
- tumor-infiltrating lymphocytes
- FoxP3+ regulatory T cell
- HLA
- MICA
Footnotes
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Grant support: Netherlands Organization for Scientific Research Zon/Mw 917.56.311 (S.H. van der Burg).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Accepted December 4, 2007.
- Received October 5, 2007.
- Revision received November 27, 2007.