Current studentsExisting staffContact us
 

Immune escape mechanisms of childhood ALL and a potential countering role for DC-like leukemia cells

Simple item page
dc.contributor.authorHan, P.
dc.contributor.authorStory, C.
dc.contributor.authorMcDonald, T.
dc.contributor.authorMrozik, K.
dc.contributor.authorSnell, L.
dc.date.issued2002
dc.description.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.
dc.description.statementofresponsibilityHan, P ; Story, C ; McDonald, T ; Mrozik, K ; Snell, L
dc.identifier.citationCytotherapy, 2002; 4(2):165-175
dc.identifier.doi10.1080/146532402317381875
dc.identifier.issn1465-3249
dc.identifier.issn1477-2566
dc.identifier.orcidMrozik, K. [0000-0002-4890-8208]
dc.identifier.urihttp://hdl.handle.net/2440/7175
dc.language.isoen
dc.publisherTaylor & Francis Ltd
dc.source.urihttps://doi.org/10.1080/146532402317381875
dc.subjectB-Lymphocytes
dc.subjectDendritic Cells
dc.subjectT-Lymphocytes
dc.subjectHematopoietic Stem Cells
dc.subjectCell Line
dc.subjectHumans
dc.subjectImmunotherapy
dc.subjectFlow Cytometry
dc.subjectCell Cycle
dc.subjectCell Differentiation
dc.subjectPrecursor Cell Lymphoblastic Leukemia-Lymphoma
dc.titleImmune escape mechanisms of childhood ALL and a potential countering role for DC-like leukemia cells
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Paediatrics publications