 |
|
Mechanisms Underlying Imiquimod-Induced Regression of Basal Cell Carcinoma In Vivo
Mirjana Urosevic, MD;
Tanja Maier, MD;
Bernd Benninghoff, PhD;
Herbert Slade, MD;
Guenter Burg, MD;
Reinhard Dummer, MD
Arch Dermatol. 2003;139:1325-1332.
Background Imiquimod is a local immune response modifier that has demonstrated potent antiviral and antitumor activity. It enhances innate and acquired immune responses via endogenous cytokine production and has proven efficacious in clearing superficial basal cell carcinoma (sBCC).
Objective To evaluate the mechanisms by which topical imiquimod treatment leads to sBCC clearance in vivo.
Design A pilot, open-label, nonrandomized study.
Setting Zurich, Switzerland.
Patients Six persons 18 years or older who had nonrecurrent primary tumors that had not undergone previous biopsy or treatment but were suitable for treatment by surgical excision. The tumors were located on the scalp, extremities, or trunk; had a minimum diameter of 1 cm and a maximum diameter of 2 cm; and were clinically and histologically consistent with sBCC.
Interventions Daily application of 5% imiquimod cream 5 times per week for a maximum of 6 weeks. When the tumor began to show signs of erosion, it was surgically excised.
Outcome Measures Parameters reflecting tumor apoptotic status (Bcl-2), expression of death receptors (Fas and Fas ligand [FasL]), intercellular adhesion molecule (ICAM) 1, immunosuppressive microenvironment (interleukin 10), and antigen presentation machinery (transporter associated with antigen presentation [TAP] 1) before and after imiquimod treatment were evaluated. The changes in the interferon  messenger RNA (mRNA) levels relative to CD4 and CD8 mRNA were assessed using quantitative polymerase chain reaction.
Results Tumor cells became more susceptible to apoptosis through decreased Bcl-2 expression after treatment with 5% imiquimod cream. Inflammatory infiltrate developed rapidly (within 3 to 5 days after treatment initiation) and was associated with the enhanced expression of ICAM-1. This early response tended to be a mixed cellular response of macrophages and lymphocytes. Interferon was produced by CD4 and CD8 T cells. Imiquimod treatment induced a massive increase in macrophage peritumoral and intratumoral infiltration. Interleukin 10 was produced by infiltrating cells but was not produced by tumor cells. Tumor expression of TAP-1 and Fas/FasL appeared to be unaffected in the first 5 days of treatment.
From the Department of Dermatology, University Hospital Zurich, Zurich, Switzerland (Drs Urosevic, Maier, Burg, and Dummer); 3M Pharmaceuticals, Neuss, Germany (Dr Benninghoff); 3M Pharmaceuticals, St Paul, Minn (Dr Slade). Drs Benninghoff and Slade are employees of 3M Pharmaceuticals.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati
What's this?
RELATED ARTICLE
Imiquimod: A Topically Applied Link Between Innate and Acquired Immunity
Daniel J. Hurwitz, Laura Pincus, and Thomas S. Kupper
Arch Dermatol. 2003;139(10):1347-1350.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Apoptotic Responses in Squamous Carcinoma and Epithelial Cells to Small-Molecule Toll-like Receptor Agonists Evaluated with Automated Cytometry
Inglefield et al.
J Biomol Screen 2006;11:575-585.
ABSTRACT
Disease-Independent Skin Recruitment and Activation of Plasmacytoid Predendritic Cells Following Imiquimod Treatment
Urosevic et al.
JNCI J Natl Cancer Inst 2005;97:1143-1153.
ABSTRACT
| FULL TEXT
Safety and Efficacy of 5% Imiquimod Cream for the Treatment of Skin Dysplasia in High-Risk Renal Transplant Recipients: Randomized, Double-blind, Placebo-Controlled Trial
Brown et al.
Arch Dermatol 2005;141:985-993.
ABSTRACT
| FULL TEXT
Treatment of Lentigo Maligna (Melanoma In Situ) With the Immune Response Modifier Imiquimod
Wolf et al.
Arch Dermatol 2005;141:510-514.
ABSTRACT
| FULL TEXT
The Pyrin Family of Fever Genes: Unmasking Genetic Determinants of Autoinflammatory Disease
Shinkai et al.
Arch Dermatol 2005;141:242-247.
FULL TEXT
Psoriasis Triggered by Toll-like Receptor 7 Agonist Imiquimod in the Presence of Dermal Plasmacytoid Dendritic Cell Precursors
Gilliet et al.
Arch Dermatol 2004;140:1490-1495.
ABSTRACT
| FULL TEXT
Imiquimod Treatment Induces Expression of Opioid Growth Factor Receptor: A Novel Tumor Antigen Induced by Interferon-{alpha}?
Urosevic et al.
Clin. Cancer Res. 2004;10:4959-4970.
ABSTRACT
| FULL TEXT
Apoptosis as a Novel Target for Cancer Chemoprevention
Sun et al.
JNCI J Natl Cancer Inst 2004;96:662-672.
ABSTRACT
| FULL TEXT
Successful Treatment of Invasive Squamous Cell Carcinoma Using Topical Imiquimod
Hengge and Schaller
Arch Dermatol 2004;140:404-406.
FULL TEXT
Imiquimod: A Topically Applied Link Between Innate and Acquired Immunity
Hurwitz et al.
Arch Dermatol 2003;139:1347-1350.
FULL TEXT
|
