Tissue macrophage response in human papillomavirus infection and cervical intraepithelial neoplasia

Abstract

Summary. Tissue macrophages in the uterine cervix were studied immunocytochemically with monoclonal antibody (MoAb) 3.9 which reacts with the majority of macrophages, and Ell which is specific for the C3b receptor, CR1. Samples from five normal women, six with human papillomavirus (HPV) infection and 10 with cervical intraepithelial neoplasia (CIN) were tested. A small population of MoAb 3.9 positive and only occasional MoAb Ell positive macrophages were found in the normal cervix. In HPV infection and CIN there was a significant infiltration of MoAb 3.9 positive and MoAb Ell positive macrophages in both the epithelium and the stroma. The pattern of infiltration in these groups of women suggests that these macrophages were most likely to be functioning as the first line of defence against the spread of the virus infection, either through a direct anti‐virus mechanism or non‐specific phagocytosis.

Disturbance of Tumor Necrosis Factor Alpha-Mediated Beta Interferon Signaling in Cervical Carcinoma Cells

“…Consequently, loss of both TNF-␣-mediated MCP-1 and IFN-␤ inducibility in tumorigenic cells concomitant with the absence of a negative regulatory effect on viral E6 and E7 expression could provide an explanation for the observed depletion of immunological effector cells in dysplastic lesions (22,29,46,60,63,64), which not only diminishes the immediate-early antiviral response but also may increase the incidence of cervical cancer. Although both E6 and E7 can counteract the function of regulatory proteins involved in the ultimate IFN response (3,40,42,48), it was amazing that tumorigenic cells still respond to exogenous IFN treatment (Fig.…”

“…Indeed, when fresh biopsies from patients were evaluated by immunohistochemistry, cervical cancer sections were found to be significantly depleted of infiltrating macrophages, T lymphocytes, and dendritic cells compared with premalignant tissue specimens (22,60,63,64). The recruitment of immunological effector cells in turn is mediated by chemokines (chemotactic cytokines) such as monocyte-chemotactic protein-1 (MCP-1) (39,45,47).…”

Interferon-? and -?, but not tumor necrosis factor-?, demonstrate immunoregulatory effects on carcinoma cell lines infected with human papillomavirus

“…In addition, high expression of this molecule on cancer cells is believed to lead to metastatic im-cells have also been reported. 49 …”

Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: The role of the chromatin structure and AP-1 composition

“…Besides disturbance of a functional Tcell surveillance (Altmann et al, 1994), dys-regulation of chemokine expression may represent another important counter-selection event during the multi-step progression to cervical cancer . Consistent with this anticipation was the recent ®nding that MCP-1 expression indeed gradually disappears in dierent stages of premalignant cervical intraepithelial neoplasias , a process, which may explain the severe reduction of intraepithelial macrophages (Tay et al, 1987) and Langerhans'cells (Spinillo et al, 1993).…”