In vivo characterization of the inflammatory infiltrate and apoptotic status in imiquimod-treated basal cell carcinoma

Vincenzo De Giorgi, Camilla Salvini, Alessandra Chiarugi, Milena Paglierani, Vincenza Maio, Paola Nicoletti, Marco Santucci, Paolo Carli, Daniela Massi

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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 tumormicro environment 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.

Original languageEnglish
Pages (from-to)312-321
Number of pages10
JournalInternational Journal of Dermatology
Issue number3
StatePublished - 2009
Externally publishedYes


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