Reduction in immune cell number and loss of 5hmC are associated with lesion grade in cervical carcinogenesis.

Abstract

Tumor genome methylation is closely related to tumor immunosuppression. In the present study, we evaluated the fluctuations in DNA methylation levels, and the numbers of infiltrating T cells and their cytokines in different-grade cervical lesions. A total of 154 human cervical specimens that included LSIL (43 cases), HSIL (48 cases), and cervical squamous cancer (63 cases) were used for this study. Immunohistochemistry for 5-hydroxymethylcytosine (5hmC) and T-cell-attracting chemokines was performed, and multiplex immunofluorescence labeling was used to identify different T-cell subtypes. We found that the proportions of samples that immunostained weakly or negatively for 5hmC were increased commensurately with elevations in the severity of cervical lesions. The expression of T-cell-attracting chemokines-including CXCL9, CXCL10, and CXCL11-was positively associated with 5hmC levels, and CXCL9 was the cytokine that was most pronounced. With the progression of cervical lesions, the numbers of total T cells, CTL, and NK cells in the cervical tissues all gradually decreased. During the occurrence and development of cervical squamous carcinoma, 5hmC was gradually lost, and immunosuppression occurred in precancerous cervical lesions.