The influence of natural killer cells in neuroblastoma
J. V. Reynolds, J. Shou, H. Choi, R. Sigal, M. M. Ziegler and J. M. Daly
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.
Human neuroblastoma (NRB) cell lines are markedly sensitive to natural
killer (NK) cell lysis in vitro, but patients with NRBs have low or absent
NK activity. This study evaluated the NK sensitivity of murine NRBs (C1300
and TBJ) in the regulation of NRB growth and determined the effects of
recombinant (r) interferon gamma and recombinant interleukin 2 (rIL-2).
Both basal (8% +/- 3% specific cytotoxicity) and induced (20% +/- 3%) NK
lyses of C1300-NRB were observed. In vivo depletion of NK cells with
anti-asialo GM-1 significantly enhanced growth of C1300-NRB and decreased
survival. Treatment with r-interferon gamma or rIL-2 on days 1 through 3
after C1300-NRB inoculation significantly prolonged the mean tumor latency
period, decreased the tumor growth rate, and enhanced in vitro NK killing
of C1300-NRB and YAC-1. The effects of r-interferon gamma and IL-2 were
abrogated by pretreatment with anti-asialo GM-1. These results demonstrated
that NK cells form one important component of regulation of a murine NRB,
but immunomodulation with potent lymphokines requires cooperation of more
than one cell type.