CD3ζ Expression and T Cell Proliferation are Inhibited by TGF-β1 and IL-10 in Cervical Cancer Patients

Abstract

Experiments with T cells from healthy donors in the presence TGF-beta1 or IL-10 suggest that these cytokines have a relevant role in T cell responses during CC progression.

Molecular Mechanism and Potential Targets for Blocking HPV-Induced Lesion Development

“…There are more tumor infiltrating T lymphocytes (TIL) in the stroma than in epithelium, in biopsies from women with SIL (including a carcinoma in situ and a normal region), and in advanced stages of the disease where CD8+ T cells prevailed [7]. Consistent with other reports [8], it was found that CD8+ T cells are predominant, compared to CD4+ T cells, in women with CC.…”

“…As expected, there was a significant correlation between low T-cell proliferation and decreased CD3 ζ mRNA expression by anti-CD3 stimulated T cells. Thus, decreased T-cell function appears to correlate with CC progression, which is in agreement with a decreased T-cell proliferation in CC patients [7]. …”

“…Consistent with other reports [8], it was found that CD8+ T cells are predominant, compared to CD4+ T cells, in women with CC. However, what are the mechanisms behind this distribution as well as behind the inability of these CD8+ T cells to eliminate the tumor in CC remains unclear [7]. …”

In vivo Antitumor Effect of an HPV-specific Promoter driving IL-12 Expression in an HPV 16-positive Murine Model of Cervical Cancer

“…In cervical cancer a predominance of the Th2-type cytokine profile is observed in association with a diminished Th1-type cytokine profile 25-28. The shift to Th2-type cytokines during the course of cervical cancer development is reflected in an increased serum concentration of Th2-type cytokines while concentration of the tumor-infiltrating T-lymphocytes decrease as the lesion progresses28-30. Therefore, upregulation of cytokines such as IL-12, which favors the development of Th1 cells, through an HPV-specific promoter represents a promising approach to induce activation of the immune response in precancerous lesions, as well as to inhibit Th2-type cytokines, in order to prevent progression of the malignancy.…”

IL-10 expression is regulated by HPV E2 protein in cervical cancer cells

“…Significantly higher interleukin (IL)-10 levels are expressed in the cervical epithelium of patients with cervical dyspasias compared to the normal cervix (3,(5)(6)(7)(8)(9). il-10 expression is directly associated with the degree of cervical lesions (6) and is correlated with the presence of HPV infection (3,10).…”