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Updated: Jul 17, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the
Monica C Panelli1, Mitchell E Stashower, Herbert B Slade
1Immunogenetics Section, Department of Transfusion Medicine, Clinical Center National Institutes of Health, Bethesda, MD 20892, USA. mpanelli@mail.cc.nih.gov
Insights
Imiquimod treatment for basal cell carcinoma (BCC) activates numerous genes, revealing early immune responses. The most effective regimen highlights pathways involved in tissue rejection and cancer immunotherapy.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Imiquimod, a Toll-like receptor-7 agonist, effectively treats basal cell carcinoma (BCC).
- Understanding early transcriptional events post-imiquimod may elucidate immune responses preceding tumor rejection.
Purpose of the Study:
- To characterize early transcriptional events induced by imiquimod in BCC patients.
- To gain insights into immunological events preceding tissue and/or tumor rejection.
Main Methods:
- Paired analysis of punch biopsies from BCC patients before and after imiquimod or vehicle treatment.
- Utilized a blinded, randomized protocol with varying imiquimod application schedules.
- Employed RNA amplification and 17.5K cDNA arrays for transcriptional profiling.
Main Results:
- All treatment schedules altered BCC transcriptional profiles; the q12h x 4 days regimen showed highest effectiveness.
- Imiquimod unequivocally stimulated 637 genes, with 539 genes indicating activation of innate and adaptive immune-effector mechanisms.
- Identified effector signatures mirroring those in cancer immunotherapy, allograft rejection, and autoimmunity.
Conclusions:
- This study provides the first human insights into early transcriptional events linked to immune rejection in a cancer eradication model.
- The findings suggest a reproducible model for studying combined innate and adaptive immune responses in tissue destruction.
- The identified pathways are likely representative of common immunological mechanisms in rejection processes.
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 x 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-alpha 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.
