title: Immunomodulation by imiquimod in patients with high-risk primary melanoma.
abstract: 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.
authors.affiliation: Division of Dermatology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Rupa
authors.initials: R
authors.lastname: Narayan
authors.forename: Hong
authors.initials: H
authors.lastname: Nguyen
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Bentow
authors.forename: Lauren
authors.initials: L
authors.lastname: Moy
authors.forename: Diana K
authors.initials: DK
authors.lastname: Lee
authors.forename: Stephanie
authors.initials: S
authors.lastname: Greger
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Haskell
authors.forename: Veena
authors.initials: V
authors.lastname: Vanchinathan
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Chang
authors.forename: Shanli
authors.initials: S
authors.lastname: Tsui
authors.forename: Tamiko
authors.initials: T
authors.lastname: Konishi
authors.forename: Begonya
authors.initials: B
authors.lastname: Comin-Anduix
authors.forename: Christine
authors.initials: C
authors.lastname: Dauphine
authors.forename: Hernan I
authors.initials: HI
authors.lastname: Vargas
authors.forename: James S
authors.initials: JS
authors.lastname: Economou
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Bruhn
authors.forename: Noah
authors.initials: N
authors.lastname: Craft
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007155:Immunologic Factors / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery; D010865:Pilot Projects; D011300:Preoperative Care / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery; D013601:T-Lymphocytes / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D007155:Immunologic Factors; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D000077271:Imiquimod