[Local immune responses in uterine cervical carcinogenesis]

In order to investigate the role of local immune response in uterine cervical carcinogenesis, lymphocyte phenotypes infiltrating the cervical region were studied by indirect immunoperoxidase staining for natural killer (NK) cells, macrophages. Langerhans cells (LC), memory T cells, CD4-positive cells and CD8-positive cells. The specimens used in this study were 9 normal ectocervical epithelium samples, 28 with mild dysplasia, 28 with moderate dysplasia, 31 with severe dysplasia and 9 with carcinoma in situ (CIS). A quantitative study was conducted in 23 patients with persistent cervical dysplasia and a comparable control group of 17 patients with regressive dysplasia. Human papillomavirus (HPV) types 16 and 18 DNA was analyzed by using polymerase chain reaction techniques, and differences in local immune responses between cases with and others without HPV types 16 and 18 were studied. The results are as follows. 1) The numbers, of NK cells and macrophages increased as the grade of cervical dysplasia increased and the numbers of these cells in cases of cervical dysplasia were greater than in normal ectocervical epithelium and CIS. 2) The numbers of LC, memory T cells and CD4-positive cells also increased with the grade of cervical dysplasia. The number of memory T cells was significantly greater in severe cervical dysplasia than in normal ectocervical epithelium or mild dysplasia (p < 0.05). 3) There were statistically significant correlations between the number of white blood cells and those of stroma-infiltrating memory T cells (r = 0.98) and CD4-positive cells (r = 0.88). A positive correlation was found between the numbers of lymphocytes in epithelium and in subepithelium. 4) A significant reduction in CD4-positive cells was founded in persistent dysplasia compared with regressive dysplasia (p < 0.05). 5) Cases with and without HPV types 16 and 18 did not differ significantly with respect to local immune responses. It is therefore considered that the increased number of lymphocytes in cervical dysplasia and the decreased number in CIS might reflect active local immunosurveillance in the process of carcinogenesis. Lymphocytes, especially CD4-positive cells, may play an important role in surveillance against the development and progression of cervical cancer.