Reversed CD4/CD8 ratios of tumor-infiltrating lymphocytes are correlated with the progression of human cervical carcinoma

Cancer. 1999 Oct 15;86(8):1537-43. doi: 10.1002/(sici)1097-0142(19991015)86:8<1537::aid-cncr21>3.0.co;2-d.

Abstract

Background: To investigate the clinical significance of tumor-infiltrating lymphocytes (TILs) within the tumor milieu of human cervical carcinoma, the authors quantitatively measured and compared the subpopulations of lymphocytes infiltrating the neoplastic cervix.

Methods: A total of 30 patients with Stage Ia-IIa cervical carcinoma were enrolled. TILs were isolated from tissue specimens by means of a mechanical dispersal technique, and the immunocyte subsets were quantified with dual-color flow cytometry. Bulky tumor was defined as tumor size >4 cm in greatest dimension according to the 1995 staging of the International Federation of Gynecology and Obstetrics.

Results: The CD4/CD8 ratios of TILs were reversed in both cervical squamous cell carcinoma (n = 20) and cervical adenocarcinoma (n = 10). The proportion of CD4(+) T cells was significantly lower in tumors from patients with lymph node metastasis (n = 8) than in those from patients without lymph node metastasis (n = 22) (24.5 vs. 32.7, P = 0.001), as was the reversed CD4/CD8 ratio (0.50 vs. 0.81, P = 0.001). The proportion of CD4(+) T cells was much lower in bulky tumors (n = 5) than in nonbulky tumors (n = 25) (21.4 vs. 32.5, P < 0.001), reflecting in a more strongly reversed CD4/CD8 ratio (0.41 vs. 0.81, P = 0.001).

Conclusions: Decreased proportions of tumor-infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma. The regional immune escape is of prognostic importance with regard to cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • CD4 Antigens / analysis
  • CD4-CD8 Ratio*
  • CD8 Antigens / analysis
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Disease Progression
  • Female
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Lymphocyte Count
  • Lymphocyte Subsets / cytology
  • Lymphocyte Subsets / immunology
  • Lymphocytes, Tumor-Infiltrating / cytology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Neoplasm Staging
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / pathology

Substances

  • CD4 Antigens
  • CD8 Antigens