Regression of lymphomatous skin deposits in a chronic lymphocytic leukemia patient treated with the Toll-like receptor-7/8 agonist, imiquimod.
The identification of clinically relevant, active immunomodulatory agents is important for developing immunotherapeutic approaches to chronic lymphocytic leukemia (CLL) and other B-cell lymphomas that are not curable with conventional chemotherapy. In this investigation, the imidazoquinoline Toll-like receptor (TLR)-7/8 agonist, imiquimod, was found to mediate the clearance of a lymphomatous skin lesion in a CLL patient. Imidazoquinolines also activated TLR-7/8 signaling pathways, resulting in increased expression of costimulatory molecules on circulating tumor cells. These observations extend the therapeutic spectrum of imiquimod to cutaneous B-cell lymphomas and suggest the use of TLR-7/8 agonists in CLL immunotherapy.
Spaner
David E
DE
Division of Molecular and Cellular Biology, Research Institute, Sunnybrook and Women's College Health Sciences Center, Toronto, Canada. spanerd@srcl.sunnybrook.utoronto.ca
Miller
Richard L
RL
Mena
Jenny
J
Grossman
Larry
L
Sorrenti
Vicki
V
Shi
Yonghong
Y
D000368:Aged; D000634:Aminoquinolines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D000077271:Imiquimod; D007167:Immunotherapy / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D051200:Toll-Like Receptor 8 / Q000819:agonists*; D016896:Treatment Outcome
D000634:Aminoquinolines; D000970:Antineoplastic Agents; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D000077271:Imiquimod