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Abstract

Background  Imiquimod use in the treatment of basal cell carcinoma (BCC) has proven to be successful in a large percentage of cases, inducing tumor regression; however, the exact cellular mechanism has not been fully clarified.

Aim  To measure the morphological changes in the tumor microenvironment and the markers of apoptosis in skin biopsies from patients with BCC before and after imiquimod treatment.

Methods  In this open label study, skin biopsies obtained from 11 patients with BCC were evaluated before and after imiquimod treatment for: (i) morphological changes in the tumor microenvironment, with specific emphasis on the immunophenotype of inflammatory cells around the tumor; and (ii) markers of apoptosis, including expression of death receptors.

Results  Imiquimod treatment induced a significant increase in the mononuclear inflammatory response. In the majority of cases, the cellular infiltrate was predominantly composed of CD3+/CD4+ T cells, suggesting that the effector response is mediated by CD3+/CD4+ lymphocytes, with a minor cytotoxic and natural killer (NK) component. An increase in the cytotoxic CD3+/CD8+ T-cell population was also observed. Imiquimod treatment was associated with a marked increased in CD20+ B cells, and a less pronounced enhancement in cells of monocyte–macrophage origin (CD68+) surrounding, or within, the tumor. This finding indicates either that macrophages play a minor role in the imiquimod-induced response, or the recruitment of these cells is related to time and dose. Imiquimod treatment decreased CD1A+ Langerhans cells in the epidermis and increased the number of CD1A+ dendritic cells within the tumor aggregates. Imiquimod reduced Bcl-2 expression, but no difference was found in Bax, Fas/FasL, and p53 expression in BCC cells.

Conclusions  Our results support the hypothesis that imiquimod activity in the treatment of BCC is partly a result of a pro-inflammatory action mediated by CD3+/CD4+ lymphoid cells and of a pro-apoptotic activity associated with decreased Bcl-2 expression.