About the cutaneous targets of bexarotene in CTCL patients.
There are several approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are one of the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. Bexarotene has been demonstrated to act on malignant T-cells by inducing their apoptosis, but nothing is known about its role on keratinocytes and Langerhans cells. Immunohistochemical analysis using CD1a, HLA-DR, ICAM-1 (activation markers), CD95 and CD40 (apoptosis markers) was conducted on frozen sections of bexarotene-exposed cutaneous explants and skin biopsy specimens from patients treated with bexarotene. None of the studied markers was significantly modulated both on cutaneous explants and on skin biopsy specimens after treatment with bexarotene, compared to controls. Langerhans cells and keratinocytes do not appear to play a central role in the therapeutic control of CTCL by bexarotene therapy. The main bexarotene's target thus remains T-cells by inducing their apoptosis, a mechanism that is different from the other retinoids used in CTCL.
Anne Chantal
AC
Knol
Gaëlle
G
Quéreux
Anabelle
A
Brocard
Fabienne
F
Ballanger
Amir
A
Khammari
Jean-Michel
JM
Nguyen
Brigitte
B
Dréno
D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018949:Antigens, CD1 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D000077610:Bexarotene; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007801:Langerhans Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology* / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D018949:Antigens, CD1; C419393:CD1a antigen; D006684:HLA-DR Antigens; D013764:Tetrahydronaphthalenes; D018799:Intercellular Adhesion Molecule-1; D000077610:Bexarotene