Dendritic Cells

Initiation of potent, effective cellular immune reactions against cancer tumor antigens requires that these antigens be presented to T-cells. This will result in activation of cytolytic T-cells by virtue of the generation of subsequent biochemical events that drive specific T-cells into clonal expansion (60). This is done by APCs, the most powerful of which is the DC. DCs residing in various epithelial tissues and the skin are characterized by the unique ability to capture antigens and migrate to draining lymph nodes, where they can activate naive and memory T-cells. Although DCs were initially found to be hard to isolate, they can now be generated in large numbers in vitro and manipulated in multiple ways before being given back to a patient to induce/augment tumor immunity. For example, the intercellular adhesion molecules play critical roles in regulating the migration and activation of both DCs and T-lymphocytes in the immune system (61).

The functional status of DCs in CLL is not yet fully delineated. However, recent reports present an overall picture of diminished function. Thus, work on blood monocytes from CLL patients has shown that functional DCs can be generated, although there may be aberrant cytokine secretion (62). Immunohistochemical staining revealed follicular DCs present in the bone marrows of patients with nodular involvement of CLL in their bone marrows (63). Our own preliminary work has found that few to none DC-like cells are generated from blood monocyte adherent populations taken from B-CLL patients. Other recent reports have shown functional defects (64) or maturation defects, including lack of CD83 and reduced expression of CD80 and HLA antigens for purified CLL DC (65). Given the potential importance of the APC to the immunodeficiencies found in B-CLL and the possible use of DCs in future vaccine-based tumor therapies, further investigation of the DC in B-CLL is warranted.

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