A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4(+)FOXP3(+) regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix

In this study, 40 biopsy samples collected from cervical cancer patients at the First Affiliated Hospital of Xi'an Jiaotong University, China, were retrospectively assessed using immunohistochemistry for CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) and were analyzed for the expression of FOXP3, OX40, granzyme B (GrB) and perforin (Prf). The proliferating index of the TILs was determined by assessing Ki67 expression. We determined the prognostic value of low and high numbers of TILs on survival by performing Kaplan-Meier analysis using median values as the cut-off points. Except for the number of CD4(+) FOXP3(+) regulatory T cells (Tregs) and the CD4/CD8 ratio, none of the CD4(+), CD8(+), OX40(+), GrB(+) or Prf(+) TILs were associated with the overall 5-year survival rate. The 5-year survival rate was significantly lower in patients who had a high percentage of Tregs as compared with the those who had a lower percentage (35.3% versus 88.9%, P=0.001), while the 5-year survival rate was significantly higher in patients with a high CD4/CD8 ratio as compared with patients who had a low CD4/CD8 ratio (82.4% versus 44.4%, P=0.029). When we considered the deaths and surviving cases as separate groups, we found that both the number of CD4(+) T cells and the CD4/CD8 ratio were significantly lower in patients who died as compared with those who survived (26.33 +/- 11.80 versus 47.79 +/- 38.18, P=0.023 and 0.60 +/- 0.25 versus 1.17 +/- 1.02, P=0.019, respectively). In conclusion, decreased proportions of tumor-infiltrating CD4(+) T cells with high percentages of Tregs and reversed CD4/CD8 ratios were significantly associated with the clinical outcome of patients with cervical carcinoma. Cellular & Molecular Immunology (2011) 8, 59-66; doi:10.1038/cmi.2010.56; published online 22 November 2010