Dendritic Cell Deficiencies in Pediatric Acute Lymphoblastic Leukemia Patients.

Acute lymphoblastic leukemia (ALL) cells are particularly poor at generating anti-leukemia immunity, despite residing in lymphoid organs. The mechanisms accounting for this phenomenon of immunoevasion are poorly understood. To assess a potential role of dendritic cells (DC) in poor anti-leukemia immunity, we analyzed peripheral blood DC in 55 pediatric ALL patients at the time of initial diagnosis and 44 age-matched healthy controls. DC were identified by their expression of HLA-DR, lack of B-, T-, NK-, and monocyte-markers, and expression of CD11c (myeloid DC) or BDCA-2 (plasmacytoid DC) using flow cytometry. T-lineage ALL patients showed normal plasmacytoid DC and significantly elevated myeloid DC (p=0.003) levels with normal expression of HLA-DR and co-stimulatory molecules. Preliminary data suggest that these DC may be less capable of stimulating allogeneic T cell responses than DC from healthy volunteers. In contrast, we found that in children with B-lineage ALL, numbers of both myeloid and plasmacytoid DC were significantly reduced (p=0.0001) as compared to healthy controls. A decrease in DC could not be explained by impaired bone marrow function, since we could not demonstrate a correlation of DC numbers with granulocyte or monocyte counts, hemoglobin levels, or platelet counts in patients with B-lineage ALL. Interestingly, in univariate analysis there was a significant correlation of lack of myeloid DC with aberrant expression of myeloid surface marker CD13 on B-lineage ALL blasts. This unexpected finding raises the hypothesis that in some cases of B-lineage ALL the physiological differentiation of a common myeloid progenitor cell might be blocked and differentiation might be skewed towards leukemia-development. No correlation of DC numbers with subtype of ALL (proB, common, preB ALL) could be demonstrated. Furthermore, in a subgroup of B-lineage ALL patients, a complete lack of plasmacytoid DCs correlated with prednisone poor response, a surrogate marker of poor prognosis. It remains currently unclear, whether lack of myeloid or plasmacytoid DC directly correlates with long-term survival. Thus, depletion of DC in B-lineage ALL patients may contribute to poor anti-leukemia immune responses in pediatric patients with ALL. Further investigations will prove whether these deficiencies may impact on patient survival and may support the concept of immunosurveillance in lymphatic malignancies.