PMID- 18381941
OWN - NLM
STAT- MEDLINE
DCOM- 20080624
LR  - 20201226
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 7
DP  - 2008 Apr 1
TI  - 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?
PG  - 2028-35
LID - 10.1158/1078-0432.CCR-07-4554 [doi]
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.
FAU - Jordanova, Ekaterina S
AU  - Jordanova ES
AD  - Department of Pathology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Gorter, Arko
AU  - Gorter A
FAU - Ayachi, Ouissam
AU  - Ayachi O
FAU - Prins, Frans
AU  - Prins F
FAU - Durrant, Lindy G
AU  - Durrant LG
FAU - Kenter, Gemma G
AU  - Kenter GG
FAU - van der Burg, Sjoerd H
AU  - van der Burg SH
FAU - Fleuren, Gert Jan
AU  - Fleuren GJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (MHC class I-related chain A)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*analysis
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - HLA-A Antigens/*biosynthesis
MH  - Histocompatibility Antigens Class I/*biosynthesis
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - Prognosis
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Uterine Cervical Neoplasms/immunology/metabolism/*mortality
EDAT- 2008/04/03 09:00
MHDA- 2008/06/25 09:00
CRDT- 2008/04/03 09:00
PHST- 2008/04/03 09:00 [pubmed]
PHST- 2008/06/25 09:00 [medline]
PHST- 2008/04/03 09:00 [entrez]
AID - 14/7/2028 [pii]
AID - 10.1158/1078-0432.CCR-07-4554 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Apr 1;14(7):2028-35. doi: 10.1158/1078-0432.CCR-07-4554.