Secondly, we also found that the proportions of CD123+DC cells (DC2) were lower in patients with cervical carcinoma in comparison with the CIN and the controls; the CIN and the controls were almost equivalent, and there was not significantly different (P > 0.05) between the
CC and the CIN. It is seemed that DC2 do not decrease noticeably in the CIN, although they were decreased in the CC like DC1. As the classic antitumor cells, DC1 were induced to apoptosis by tumor if there was no tumor intervention or enhancement of DC1. The loss of DC1 thus correlates with tumor burden. DC2 possessing both antitumor and immunosuppression displayed a little differently in process of tumor. The side of immunosuppression may permit or promote the development of tumor [33, 34]. Our findings indicate that, in cervical carcinoma patients, decreased numbers of these cells closely correlate with disease stage and tumor progression. The decrease in circulating DCs may have functional selleckchem RG7420 ic50 consequences on the production of cytokines and on antigen presentation to naive T-cells. The reason for the decreased frequency of these two subsets of DCs in patients with CC remains unknown. It may be that tumors induce apoptosis in DCs by direct
contact, or tumors may inhibit the differentiation of DCs in vivo by secreting soluble factors. Several studies have demonstrated that DCs in tumor patients are not able to induce primary T-cell responses. Antigen-specific Treg cells were over-represented at tumor sites and mediated antigen-specific, local, immune suppression, thus inhibiting the function of anti-cancer T effector cells [37, 38]. We showed that the DCs upregulated their MHC class II molecules (HLA-DR) in response to tumor-associated antigens, although DCs from patients with CC and CIN exhibit more upgraded HLA-DR
than controls. However, the level is moderated, which is different from other studies(29,36). Lee et al. found that in women with human papillomavirus (HPV)-related cervical squamous intraepithelial lesions (SILs) or atypical squamous cells of undetermined significance (ASCUS), peripheral blood DC1 and monocyte-derived dendritic cells (MDDCs), but Staurosporine concentration not DC2 cells, expressed low levels of HLA-DR [39]. In our study, there is no significant difference in HLA-DR between the CIN groups and the controls, but in the CC group, the expression of HLA-DR increased. HPV DNA is found in 90% of all cervical cancers. DC2 can be activated by this virus, which causes them to undergo maturation. This process enhances their antigen presentation potential by upregulating MHC class II molecules. However, even in fully mature DC2 cells, levels of MHC II and costimulatory molecules remain significantly lower than in DC1 cells [40]. This may be the reason that the expression of HLA-DR increased and the level is moderated. In addition, all circulating dendritic cell subsets exhibited low CD80 and CD86 expression, which is concordant with other reports [29, 41].