Widely disseminated
neuroblastoma in children older than infancy remains a very poor prognosis disease. Even the introduction of marrow ablative
chemotherapy with autologous rescue has not significantly improved the outlook for these children, presumably because of a failure to eradicate
minimal residual disease. One additional approach which may hold promise is the use of
immunomodulation with
cytokines such as
IL2 in the setting of
minimal residual disease (MDR), for example after intensive
chemotherapy and ABMT. However, considerable variability in the susceptibility of
neuroblastoma cells to natural killer (NK) and lymphokine-activated (LAK) killing has been observed, and it is presently unclear how NK and LAK cells recognise
neuroblastoma cells. In this paper we examine expression of
cell adhesion molecules on
neuroblastoma to determine which of these modify interaction with NK and LAK cells. We find that
LFA-3 (CD58), the
ligand for CD2 is of predominant importance in predicting susceptibility of
neuroblastoma to the cytotoxic actions of NK and LAK cells, while expression of
ICAM-1 (CD54) may also modify susceptibility. These findings were confirmed by blocking experiments in which co-culture of target cells with
ICAM-1 and
LFA-3 reduced LAK and NK cytotoxicity. Study of the immunophenotypic features of each patient's
neuroblastoma cells before induction of MRD may be valuable in determining the likely effect of
IL2 in predicting disease reactivation.