Reversed CD4/CD8 ratios of tumor-infiltrating lymphocytes are correlated with the progression of human cervical carcinoma.
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.
Sheu
B C
BC
Department of Obstetrics and Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan.
Hsu
S M
SM
Ho
H N
HN
Lin
R H
RH
Torng
P L
PL
Huang
S C
SC
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008207:Lymphatic Metastasis; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology*; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology
D015704:CD4 Antigens; D016827:CD8 Antigens