Abstract
Patients with B-type chronic lymphocytic leukemia (B-CLL) segregate into 2 subgroups based on the mutational status of the immunoglobulin (Ig) V genes and the patients in these subgroups follow very different clinical courses. To examine whether dendritic cells (DCs) generated from CLL patients can be candidates for immune therapy, we compared the phenotypic and functional capacities of DCs generated from patients of the 2 CLL subgroups (normal age-matched subjects [normal-DCs]). Our data show that immature DCs from B-CLL patients (B-CLL-DCs) have the same capacity to take up antigen as those from normal controls. Furthermore, B-CLL-DCs generated from the 2 CLL subgroups up-regulated MHC-II, CD80, CD86, CD83, CD40, and CD54 and down-regulated CD206 in response to stimulation with a cocktail of cytokines (CyC) and secreted increased levels of tumor necrosis factor alpha, interleukin (IL)-8, IL-6, IL-12 (p70), and RANTES in a manner typical of mature normal-DCs. Interestingly, CD54 was significantly more up-regulated by CyC in B-CLL-DCs compared with normal-DCs. Except for CD54, no significant differences in surface molecule expression were observed between normal-DCs and B-CLL-DCs. B-CLL-DCs from both subgroups, including 6 patients with VH1-69, that usually fare poorly, presented tetanus toxoid to autologous T cells in vitro similar to normal- DCs. Our data show that DCs generated from the B-CLL subgroup with unmutated Ig V genes are functionally normal. These results are very promising for the use of DCs from patients with poor prognosis for immunotherapy.
Highlights
B cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the Western world
At 37°C, no difference was observed between the percentages of cells that had taken up dextran-fluorescein isothiocyanate (FITC) in B-CLLDCs or normal-dendritic cells (DCs), indicating that DCs generated from these patients have normal endocytic functions for soluble proteins
When the B-CLL patients were divided into the 2 subgroups, mature DCs from patients with mutated B-CLL showed significantly higher expression of CD54 compared with normal donors
Summary
B cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the Western world. 7500 people develop the disease annually and about 5000 die of the disease each year [1]. To date there is no curative therapy for B-CLL [2]. The development of new strategies to attack re-emerging clones after classic therapy is necessary. B-CLL patients can be divided into 2 subgroups based on immunoglobulin variable gene (Ig V) mutational status. Others and we have shown that Ig mutation status [3,4] and CD38 expression [5] segregate patients into 2 subgroups that follow very different clinical courses [5,6]
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