Sézary syndrome is a cutaneous T cell lymphoma characterized by infiltration of the skin by CD4+ cells. These cells generally respond poorly to mitogens and T cell activators. We have studied the ...action of IL1 to IL4, IL6, and IL7 on the proliferation of Sézary cells from 12 patients. With the exception of IL2 and IL7, the cytokines studied had no proliferative effect on these cells. Whereas IL2 had only a low proliferative capacity (two- to threefold increase) on peripheral blood mononuclear cells, recombinant IL7 constantly induced a very significant (3-40-fold increase) proliferative response, and was used successfully to generate cell lines in three out of eight cases. Growth of Sézary cell lines was shown to be strictly dependent on IL7, and after 2-5 wk of culture presented a switch to a homogeneous phenotype CD3+4+8-7- (except for one line that remained CD7+), with a typical morphology of Sézary cells. Their tumoral origin was demonstrated by the expression of the same T cell receptor-beta gene rearrangement as the patients' T cells. Importantly, cultured normal epidermal keratinocyte supernatants could support the growth of our Sézary lines. Furthermore, the proliferative activity contained in these supernatants was completely blocked by a monoclonal anti-IL7 antibody. These results suggest that IL7 may, therefore, represent an important cytokine in the physiopathology of cutaneous T cell lymphoma.
To describe clinicopathologic features and to identify prognostic factors in a large series of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT), as defined in the recent World ...Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas.
Retrospective multicenter study from the French Study Group on Cutaneous Lymphomas.
Nineteen departments of dermatology in 10 regions of France.
Sixty patients with a PCLBCL LT included in the registry of the French Study Group on Cutaneous Lymphomas.
Age, sex, outcome, therapy, B symptoms, cutaneous extent, number of lesions, location (leg vs nonleg), serum lactate dehydrogenase level, and MUM-1 and Bcl-2 expression were recorded. Disease-specific survival was used as the main end point. Prognostic factors were identified using a Cox proportional hazards model.
Primary cutaneous diffuse large B-cell lymphoma, leg type is characterized by a predilection for the leg (72%), a high proportion of Bcl-2 expression (85%), an advanced age at onset (mean age, 76 years), and frequent relapses and extracutaneous dissemination. The overall 5-year disease-specific survival rate was 41%. Location on the leg and multiple skin lesions were predictive of death in multivariate analysis. Although no variable related to therapy was significantly associated with survival, patients recently treated with combinations of anthracycline-containing chemotherapies and rituximab had a more favorable short-term outcome.
Primary cutaneous diffuse large B-cell lymphoma, leg type is a distinct entity with a poor prognosis, particularly in patients with multiple tumors on the legs. Despite the advanced age of many patients, the prognosis could be improved with combinations of anthracycline-containing chemotherapies and rituximab.
Using a newly generated monoclonal antibody we identified the 96 kDa transmembrane receptor SC5 expressed simultaneously on a human Sezary cell line and a minor T cell subset in normal individuals. ...SC5 antigen was detected mostly on CD45RO+ lymphocytes from both CD4+ and CD8+ subsets as well as on natural killer and B lineage cells. SC5 surface expression increased very early after polyclonal stimulation of CD3+ cells due to the transfer of intracellular SC5 molecules to the cell membrane. Engagement of SC5 receptor by its monoclonal antibody inhibited the anti-CD3-induced proliferation and cytokine secretion of peripheral blood T cells and cell clones, whereas SC5 monoclonal antibody did not affect the cytotoxic activity of CD8+ T cell clones. Extensive phenotypic analysis revealed that the percentage of SC5+ CD4+ circulating lymphocytes in Sezary syndrome patients was significantly increased in comparison with controls (p < 0.01) and correlated with the morphologically detected percentage of Sezary syndrome cells in peripheral blood (p < 0.001). In one patient we clearly demonstrated that the circulating malignant T cells coexpress SC5 molecules. Importantly, ligation of SC5 receptor in a cutaneous T cell lymphoma cell line profoundly inhibited the anti-CD3-induced proliferation. Consequently, the expression of SC5 receptor in the peripheral blood of Sezary syndrome patients may serve not only to detect the presence of circulating malignant CD4+ cells but also as a target for immunotherapy.
Inhibitory receptors on natural killer cells and on a minority of T lymphocytes are major histocompatibility complex class Ia or Ib specific. We have previously reported several tumor-specific ...cytotoxic T cell clones infiltrating a CD4+ Vβ13+ cutaneous T cell lymphoma. These clones mediated a specific major histocompatibility complex class I-restricted cytotoxic activity toward the uncultured tumor cells and autologous long-term tumor T cell lines. In this study, we cultured with interleukin-2 the peripheral blood lymphocytes of the same patient a few weeks before invasion of the blood by tumor cells. We report the rapid and selective expansion of a CD8+ Vβ13+ lymphoid population. This population was clonal, as it expressed a unique T cell receptor-Vβ junctional region. Vβ13+ tumor cells and Vβ13+ reactive T cells were shown to have different junctional sequences. The CD8+ reactive clone was functional, as it had a specific autologous tumor-specific, human leukocyte antigen-A2 restricted, cytotoxic activity. This clone coexpressed high levels of CD158a, CD158b, p70, and CD94/NKG2A inhibitory receptors. Interestingly, we found that anti-CD158a and anti-CD158b monoclonal antibodies could inhibit anti-CD3 redirected cytotoxicity mediated by the reactive clonal population. Further, an anti-human leukocyte antigen-B/C monoclonal antibody enhanced the specific cytotoxic activity of the clone against autologous tumor cells. These results are the first evidence that inhibitory receptor expression can lead to the inhibition of cutaneous T cell lymphoma-specific T cell responses.
Specific cutaneous lesions of Waldenström macroglobulinemia are rare and include neoplastic cell infiltrates, IgM bullous disease, and so-called IgM-storage papules, which characterize cutaneous ...macroglobulinosis (CM).
We report 2 patients with CM. In patient 1, CM started as small papules, as reported in most of the previously published case studies of CM. In patient 2, lesion evolution was remarkable by its severity, with large ulcerated nodules, and the disease progressed rapidly. As mentioned for half the previously described patients, peripheral neuropathy was suspected in patient 2 and demonstrated in patient 1, with production of antibodies to myelin-associated glycoprotein.
To the best of our knowledge, rituximab treatment of Waldenström macroglobulinemia associated with CM has not been described previously. Rituximab caused complete remission of the lesions in patient 1, whereas disease rapidly progressed in patient 2, and the patient died. These observations suggest that evolution of the cutaneous IgM-storage lesions reflects that of the underlying Waldenström macroglobulinemia, and CM is not a prognostic marker.
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