Toll receptor agonist therapy of skin cancer and cutaneous T-cell lymphoma.
OBJECTIVE
The use of agents which exhibit the ability to potently activate the innate immune response has gained significant interest as therapeutics to treat cancer. We will review the history and the current applications of these agents to treat skin cancer and cutaneous T-cell lymphoma.


RESULTS
Particular attention has been focused upon Toll-like receptor (TLR) agonists, including imidazoquinolines, which can trigger TLR 7 and TLR 8, and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides, which activate TLR 9-expressing cells. Imiquimod, a TLR 7 agonist, has been found to be efficacious for basal cell and squamous cell cancers, as well as cutaneous T-cell lymphoma and lentigo maligna melanoma. CpGs have demonstrated efficacy for cutaneous T-cell lymphoma. Additional more potent compounds, including resiquimod, are presently in clinical trials for several types of skin cancers.


CONCLUSIONS
TLR agonists that can activate the innate immune response have been used to treat a variety of skin cancers including basal cell cancer, squamous cell cancer, lentigo maligna melanoma and cutaneous T-cell lymphoma. Significant clinical efficacy has been observed for all of these conditions. It is anticipated that additional members of the TLR agonist family will be available in the clinic for the future treatment of skin cancers as well as other malignancies.
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Auris O
AO
Huen
Alain H
AH
Rook
D000634:Aminoquinolines / Q000627:therapeutic use; D006801:Humans; D000077271:Imiquimod; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use; D011806:Quinolinium Compounds / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology / Q000378:metabolism
D000634:Aminoquinolines; D009838:Oligodeoxyribonucleotides; D011806:Quinolinium Compounds; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D000077271:Imiquimod