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.
Department of Dermatology, University of Pennsylvania, 245 CRB, 415 Curie Blvd, Philadelphia, PA 19104, USA. mwysocka@mail.med.upenn.edu
Maria
M
Wysocka
Bernice M
BM
Benoit
Sarah
S
Newton
Livio
L
Azzoni
Luis J
LJ
Montaner
Alain H
AH
Rook
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