Enhancement of the host immune responses in cutaneous T-cell lymphoma by CpG oligodeoxynucleotides and IL-15.
Patients with advanced cutaneous T-cell lymphoma (CTCL) exhibit profound defects in cell-mediated immunity. Host immune functions appear to play an integral role in mediating disease-controlling responses in CTCL, therefore we investigated the effects of synthetic oligode-oxynucleotides with CpG motifs (CpG ODN), which have been recognized as immune stimulatory by virtue of activation of dendritic cells (DCs) following binding to Toll-like receptor (TLR) 9. Peripheral blood mononuclear cells (PBMCs) from patients with advanced CTCL (erythroderma with circulating malignant T cells) and healthy volunteers were cultured with either CpG-A or CpG-B ODN. Patients' PBMCs exhibited marked induction of interferon-alpha (IFN-alpha) release following culture with CpG-A. Similarly significant activation of NK cells and CD8 T cells occurred as assessed by up-modulation of CD69 expression and by natural killer lytic activity. Nevertheless, the PBMCs of patients exhibited blunted responses to CpG-A compared to healthy volunteers. In such cases, IL-15 was capable of producing levels of NK activation that were superior to CpG-A, while the combined effects of CpG-A plus IL-15 induced maximal activation of NK cells and further enhanced activation of CD8 T cells. These findings have important implications for the potential enhancement of antitumor immunity among patients with advanced CTCL.
Wysocka
Maria
M
Department of Dermatology, University of Pennsylvania, 245 CRB, 415 Curie Blvd, Philadelphia, PA 19104, USA. mwysocka@mail.med.upenn.edu
Benoit
Bernice M
BM
Newton
Sarah
S
Azzoni
Livio
L
Montaner
Luis J
LJ
Rook
Alain H
AH
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D019409:Interleukin-15 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology*; D012751:Sezary Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015226:Dinucleoside Phosphates; D019409:Interleukin-15; C015772:CpG dinucleotide