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Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection

Monica C Panelli1, Mitchell E Stashower2, Herbert B Slade3, Kina Smith1, Christopher Norwood4, Andrea Abati5, Patricia Fetsch5, Armando Filie5, Shelley-Ann Walters3, Calvin Astry3, Eleonora Aricó1, Yingdong Zhao6, Silvia Selleri17, Ena Wang1 and Francesco M Marincola1*

Author Affiliations

1 Immunogenetics Section, Department of Transfusion Medicine, Clinical Center National Institutes of Health, Bethesda, MD 20892, USA

2 The Clinical Skin Center of Northern Virginia, Fairfax, VA 22033, USA

3 3M Pharmaceuticals, St Paul, MN 55144-1000, USA

4 Department of Dermatology, National Naval Medical Center, Bethesda, MD 20889, USA

5 Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA

6 Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA

7 Universita' degli Studi di Milano, Department of Human Morphology, via Mangiagalli, 20133 Milan, Italy

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Genome Biology 2007, 8:R8  doi:10.1186/gb-2007-8-1-r8

Published: 15 January 2007



Imiquimod is a Toll-like receptor-7 agonist capable of inducing complete clearance of basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization of the early transcriptional events induced by imiquimod may provide insights about immunological events preceding acute tissue and/or tumor rejection.


We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (n = 22) or vehicle cream (n = 14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hours for 4 or 8 days). RNA was amplified and hybridized to 17.5 K cDNA arrays. All treatment schedules similarly affected the transcriptional profile of BCC; however, the q12 × 4 days regimen, associated with highest effectiveness, induced the most changes, with 637 genes unequivocally stimulated by imiquimod. A minority of transcripts (98 genes) confirmed previous reports of interferon-α involvement. The remaining 539 genes portrayed additional immunological functions predominantly involving the activation of cellular innate and adaptive immune-effector mechanisms. Importantly, these effector signatures recapitulate previous observations of tissue rejection in the context of cancer immunotherapy, acute allograft rejection and autoimmunity.


This study, based on a powerful and reproducible model of cancer eradication by innate immune mechanisms, provides the first insights in humans into the early transcriptional events associated with immune rejection. This model is likely representative of constant immunological pathways through which innate and adaptive immune responses combine to induce tissue destruction.