Implication of different effector mechanisms by cord blood-derived and peripheral blood-derived cytokine-induced killer cells to kill precursor B acute lymphoblastic leukemia cell lines.

BACKGROUND AIMS

Cytokine-induced killer (CIK) cells ex vivo-expanded from cord blood (CB) or peripheral blood (PB) have been shown to be cytotoxic against autologous and allogeneic tumor cells. We have previously shown that CD56(+) CIK cells (CD3(+)CD56(+) and CD3(-)CD56(+)) are capable of killing precursor B-cell acute lymphoblastic leukemia (B-ALL) cell lines. However, the lytic pathways used by CD56(+) PB and CB-CIK cells to kill B-ALL cell lines have not been studied.

METHODS

CB and PB-CIK cells were differentiated. CD56(+) CB- and PB-CIK cells were compared for expression of different phenotypic markers and for the lytic pathways used to kill B-ALL cell lines.

RESULTS

We found that cytotoxic granule proteins were expressed at higher levels in CD56(+) PB-CIK than in CD56(+) CB-CIK cells. However, CD56(+) CB-CIK cells expressed more tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) compared with CD56(+) PB-CIK cells. We observed that CD56(+) CB-CIK cells used both the NKG2D and TRAIL cytotoxic pathways and were more effective at killing REH cells than CD56(+) PB-CIK cells that used only the NKG2D pathway. In contrast, CD56(+) PB-CIK cells used both NKG2D and TRAIL pathways to kill NALM6 cells, whereas CD56(+) CB-CIK cells used only the NKG2D pathway.

CONCLUSIONS

Our results suggest that both the source of CIK and the type of B-ALL cell line have an impact on the intensity of the cytolytic activity and on the pathway used. These findings may have clinical implications with respect to optimizing therapeutic efficacy, which may be dependent on the source of the CIK cells and on the target tumor cells.