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Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Authors:
Rupa Narayan Hong Nguyen Jason J Bentow Lauren Moy Diana K Lee Stephanie Greger Jacquelyn Haskell Veena Vanchinathan Pei-Lin Chang Shanli Tsui Tamiko Konishi Begonya Comin-Anduix Christine Dauphine Hernan I Vargas James S Economou Antoni Ribas Kevin W Bruhn Noah Craft

J Invest Dermatol 2012 Jan 18;132(1):163-9. Epub 2011 Aug 18.

Division of Dermatology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted.

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http://dx.doi.org/10.1038/jid.2011.247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229834PMC
January 2012

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