Authors: Anna De Geer LenaMaria Carlson Per Kogner Jelena Levitskaya
Publish Date: 2007/10/26
Volume: 57, Issue: 5, Pages: 731-743
Abstract
Neuroblastoma NB is often described as an unfavorable target for both HLArestricted and death receptormediated elimination by cytotoxic T lymphocytes CTLs due to low or absent HLA class I and caspase8 expression We investigated the effects of soluble factors released by CTLs activated by TCR triggering named as activated supernatant AS on the levels and composition of cell surface molecules involved in HLArestricted and HLAindependent NB cell recognition surface immune phenotype Using a panel of longterm propagated NB cell lines and freshly isolated primary human NB cells we analyzed surface expression of the 1 cognate receptors for TNFα Fas and TRAIL 2 HLA class I and II heterodimers 3 adhesion molecules 4 the intracellular expression and activation of caspase8 as well as 5 the susceptibility of NB cells to death receptormediated killing prior to and after exposure to AS The exposure of NB cells to soluble factors released by activated CTLs skewed the surface immune phenotype of both long term cultured and primary NB cells induced the expression and activation of caspase8 and increased the susceptibility of tumor cells to lysis by TRAIL and Fasagonistic antibody Blocking experiments identified IFNγ and TNFα as main factors responsible for modulating the surface antigens of NB cells by AS Our data suggest that recruitment of CTLs activated on third party targets into the vicinity of the NB tumor mass may override the “silent” immune phenotype of NB cells via the action of soluble factors
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