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

Background 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. Methods To study the effect of ALL cells on T-cell function, ALL cells were incubated with T adult cells activated by OKT3 MAb. Liquid clture of de novo pre-B ALL cells for 7 days, in a medium containing IL-1, 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. Results 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. Discussion DC-like cells can be generated from childhood pre-B ALL cells and are potent stimulators of adult and naive cord CD8(+) T cells via CD4(+) cells. These cells may form part of an immunotherapy strategy to overcome tolerance to ALL cells.