MECHANISMS OF SELECTIVE KILLING OF NEUROBLASTOMA-CELLS BY NATURAL-KILLER-CELLS AND LYMPHOKINE-ACTIVATED KILLER-CELLS - POTENTIAL FOR RESIDUAL DISEASE ERADICATION

Widely disseminated neuroblastoma in children older than infancy remai ns a very poor prognosis disease. Even the introduction of marrow abla tive chemotherapy with autologous rescue has not significantly improve d the outlook for these children, presumably because of a failure to e radicate minimal residual disease. One additional approach which may h old promise is the use of immunomodulation with cytokines such as IL2 in the setting of minimal residual disease (MDR), for example after in tensive chemotherapy and ABMT. However, considerable variability in th e susceptibility of neuroblastoma cells to natural killer (NK) and lym phokine-activated (LAK) killing has been observed, and it is presently unclear how NK and LAK cells recognise neuroblastoma cells. In this p aper 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 impor tance in predicting susceptibility of neuroblastoma to the cytotoxic a ctions of NK and LAK cells, while expression of ICAM-1 (CD54) may also modify susceptibility. These findings were confirmed by blocking expe riments in which co-culture of target cells with ICAM-1 and LFA-3 redu ced LAK and NK cytotoxicity. Study of the immunophenotypic features of each patient's neuroblastoma cells before induction of MRD may be val uable in determining the likely effect of IL2 in predicting disease re activation.