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|Title:||Immune escape mechanisms of childhood ALL and a potential countering role for DC-like leukemia cells|
|Citation:||Cytotherapy, 2002; 4(2):165-175|
|Publisher:||Taylor & Francis Ltd|
|Han, P ; Story, C ; McDonald, T ; Mrozik, K ; Snell, L|
|Abstract:||<h4>Background</h4>Pre-B ALL cells generally elicit a weak immune host response, due to poor expression of co-stimulatory molecules and/or suppression of immune function. A possible way to enhance immunogenicity of pre-B ALL cells is to convert them to DC-like cells.<h4>Methods</h4>To study the effect of ALL cells on T-cell function, ALL cells were incubated with T adult cells activated by OKT3 MAb. Liquid culture of de novo pre-B ALL cells for 7 days, in a medium containing IL-1alpha, IL-3, IL-7, Flt 3 ligand (L) and tumor-necrosis factor alpha (TNF-alpha) produced DC-like cells. These were evaluated for morphology, viability, phenotype, as measured by flow cytometry, and function, including MLR.<h4>Results</h4>Pre-B ALL cell-lines NALM-6, BALM and de novo pre-B ALL cells failed to stimulate T cells, but suppressed stimulated T cells. The DC-like cells displayed characteristic features of DCs: filiform cytoplasmic projections, and phenotypic expression of co-stimulatory molecules CD80/86, MHC Class I and II molecules, CD83 and CD1a. Genetic monoclonality study confirmed their leukemic origin. In a 5-day MLR culture, the DC-like cells potently activated allogeneic adult and cord CD4+ and CD8+ T cells. Furthermore, both CD4+ and CD8+ T cells were primed towards a Type I. No such effect was seen with unmanipulated de novo pre-B ALL cells.<h4>Discussion</h4>DC-like cells can be generated from childhood pre-B ALL cells and are potent stimulators of adult and naïve cord CD8+ T cells via CD4+ cells. These cells may form part of an immunotherapy strategy to overcome tolerance to ALL cells.|
|Keywords:||B-Lymphocytes; Dendritic Cells; T-Lymphocytes; Hematopoietic Stem Cells; Cell Line; Humans; Immunotherapy; Flow Cytometry; Cell Cycle; Cell Differentiation; Precursor Cell Lymphoblastic Leukemia-Lymphoma|
|Appears in Collections:||Paediatrics publications|
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