Abstract
The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.
Highlights
The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold
Imiquimod significantly decreases number of AKs. 19 patients with confirmed histological diagnosis of AK were included in the final analysis (Table 1)
All patients had a history of prior AK and the treated lesions were located on the scalp (n = 11) and face (n = 8)
Summary
The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. Abbreviations AKs Actinic keratoses SCC Squamous cell carcinomas BCC Basal cell carcinoma MM Maligant melanoma CR Complete responder IR Incomplete responder. Actinic Keratoses (AKs) are dysplasias of the epidermis that are associated with an increased risk for squamous cell carcinoma (SCC)[1]. It is difficult to predict whether AK will progress to SCC, but there is a greater than six-fold increase in the risk of developing skin cancers with the presence of A Ks5,6. AKs have been shown to be markers of field cancerization in excised basal cell carcinoma (BCC), SCC, and malignant melanoma (MM) s pecimens[8]. Topical imiquimod is a field treatment for AK shown to lead to initial clearance rates of 85%. Imiquimod is an agonist for toll-like receptor 7, which is commonly involved in pathogen recognition and leads to downstream activation of nuclear factor kappa B and induction of pro-inflammatory Th1 cytokines including interferon alpha, tumor necrosis factor alpha, and various interleukins[10,11,12,13,14]
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