Serum vascular endothelial growth factor A levels reflect itch severity in mycosis fungoides and Sézary syndrome

Angiogenesis is an important step to support progression of malignancies, including mycosis fungoides (MF) and Sézary syndrome (SS). Vascular endothelial growth factor (VEGF)‐A, a key player in angiogenesis, is secreted by tumor cells of MF/SS and its expression levels in lesional skin correlated with disease severity. In this study, we examined serum VEGF‐A levels in MF/SS patients. Serum VEGF‐A levels were elevated in patients with erythrodermic MF/SS and the levels decreased after treatment. Importantly, serum VEGF‐A levels positively correlated with markers for pruritus. We also found that VEGF‐A upregulated mRNA expression of thymic stromal lymphopoietin by keratinocytes. Taken together, our study suggests that VEGF‐A can promote progression and pruritus in MF/SS. Inhibition of VEGF‐A signaling can be a therapeutic strategy for patients with erythrodermic MF/SS.     

Decreased IL-10-producing regulatory B cells in patients with advanced mycosis fungoides

Background

Historically, B cells have been considered as positive regulators of humoral immune responses. Specific B-cell subsets, however, negatively regulate immune responses and are termed “regulatory B cells” (Bregs). Recently, Bregs have been linked to not only inflammatory and autoimmune diseases, but also malignancies via suppressing antitumour immunity.

Objectives

To investigate the involvement of Bregs in advanced mycosis fungoides (MF).

Materials&Methods

The frequency ofCD19⁺CD24^hiCD27⁺ memoryBcells andCD19⁺CD24^hiCD38^hi transitional B cells (which enrich IL-10-producing Bregs) was examined in peripheral blood from patients with advanced MF (n = 11) and healthy controls (n = 9) by flow cytometry. The frequency of IL-10-producing Bregs was also measured by flow cytometry. The correlation between frequency or number of B-cell subsets and disease severity markers was also analysed.

Results

The frequency of CD19⁺CD24^hiCD27⁺ B cells, CD19⁺CD24^hiCD38^hi B cells, and IL-10-producing B cells was decreased in peripheral blood of advanced MF patients. The frequency and number of these B-cell subsets inversely correlated with serum soluble IL-2 receptor and serum lactate dehydrogenase levels.

Conclusions

The development of IL-10-producing Bregs is impaired in patients with advanced MF and a decrease in IL-10-producing Bregs may play an important role in the progression of advanced MF.

     

The in vitro generation of Ph1+ ALL-specific HLA-A24-restricted cytotoxic T lymphocytes using a synthetic 16 mer minor bcr-abl peptide

Sixteen mer peptide, which spans the junctional region of the acute lymphoid leukemia (ALL)-specific minor bcr-abl fusion protein and contains a motif that can bind to human leukocyte antigen (HLA)-A24, was constructed. We tried to generate Philadelphia chromosome 1 (Ph1) positive ALL-specific cytotoxic T lymphocytes (CTLs) from eight normal HLA-A24+ individuals with peptide-pulsed autologous dendritic cells (DCs). CTLs could be generated from the mononuclear cells (MNCs) of a single donor, which could kill peptide-pulsed autologous DCs and two A24+ ALL lines, while an HLA-A24+ CML line was only weakly killed and unpulsed DCs or the control lines Daudi or K562 were not recognized. Those CTLs consisted predominantly of CD8+ T cells whose cytotoxicity could be neutralized by monoclonal antibodies to HLA-class I or HLA-A24, and also produced interferon (IFN)-gamma after being stimulated with peptide-pulsed DCs.