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

Monica C. Panelli, Mitchell E. Stashower, Herbert B. Slade, Kina Smith, Christopher Norwood, Andrea Abati, Patricia Fetsch, Armando Filie, Shelley Ann Walters, Calvin Astry, Eleonora Aricó, Yingdong Zhao, Silvia Selleri, Ena Wang, Francesco M. Marincola

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Abstract

Background: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Article numberR8
JournalGenome Biology
Volume8
Issue number1
DOIs
Publication statusPublished - 15 Jan 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Panelli, M. C., Stashower, M. E., Slade, H. B., Smith, K., Norwood, C., Abati, A., Fetsch, P., Filie, A., Walters, S. A., Astry, C., Aricó, E., Zhao, Y., Selleri, S., Wang, E., & Marincola, F. M. (2007). Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection. Genome Biology, 8(1), [R8]. https://doi.org/10.1186/gb-2007-8-1-r8