Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream

Abstract

BackgroundThe objective of this study was to identify the molecular processes responsible for the anti-lesional activity of imiquimod in subjects with actinic keratosis using global gene expression profiling.MethodsA double-blind, placebo-controlled, randomized study was conducted to evaluate gene expression changes in actinic keratosis treated with imiquimod 5% cream. Male subjects (N = 17) with ≥ 5 actinic keratosis on the scalp applied placebo cream or imiquimod 3 times a week on nonconsecutive days for 4 weeks. To elucidate the molecular processes involved in actinic keratosis lesion regression by imiquimod, gene expression analysis using oligonucleotide arrays and real time reverse transcriptase polymerase chain reaction were performed on shave biopsies of lesions taken before and after treatment.ResultsImiquimod modulated the expression of a large number of genes important in both the innate and adaptive immune response, including increased expression of interferon-inducible genes with known antiviral, anti-proliferative and immune modulatory activity, as well as various Toll-like receptors. In addition, imiquimod increased the expression of genes associated with activation of macrophages, dendritic cells, cytotoxic T cells, and natural killer cells, as well as activation of apoptotic pathways.ConclusionData suggest that topical application of imiquimod stimulates cells in the skin to secrete cytokines and chemokines that lead to inflammatory cell influx into the lesions and subsequent apoptotic and immune cell-mediated destruction of lesions.

The Toll-Like Receptor Agonist Imiquimod Is Active against Prions

“…IQ has potent antiviral and antitumor properties and is used in a large diversity of cutaneous diseases like warts on the skin of the genital and anal areas [18], and is also used to treat actinic keratoses, a skin condition of the face and scalp, and superficial basal cell carcinoma a type of skin cancer [19,20]. IQ does not show a direct activity against the viruses that cause warts [21]. It appears to act via activation of the local innate immune response, through Toll-like receptor 7 (TLR7) stimulation.…”

Patient satisfaction and reported outcomes on the management of actinic keratosis

“…Such a response enhances interferon (IFN), tumor necrosis factor (TNF), and interleukins 1 and 12 (IL-1/12) and further stimulates an acquired immune response through the activation of TH1 cells 18. Topical application of imiquimod induces IFNα within AK lesions and subsequently triggers such innate and adaptive immune response 19. An open-label, multicenter study with 118 AK patients utilized the Skin-dex-17 and TSQM surveys to assess how treatment with imiquimod cream 5% impacts patient-reported outcomes and health-related QoL (HRQoL) and found no clinically relevant impact 20.…”

Roles of the immune system in skin cancer

“…Imiquimod is clinically effective against superficial primary skin tumours and cutaneous metastases 190 , including BCC, Bowen’s disease, erythroplasia de Queyrat, and lentigo maligna 191 . Imiquimod activates Toll-like receptor (TLR) 7 on plasmacytoid DCs, causing the NF-κβ-dependent secretion of pro-inflammatory cytokines such as IFN-γ and the chemokines CXCR3, CXCL10, CXCL11, and CCL8 that collectively regulate lymphocyte trafficking 192–194 . This results in further activation of antigen-presenting cells and enhancement of Th1 and cytotoxic CD8+ T-cell responses 194–196 .…”