The liver and immunoregulation of neuroblastoma growth

C1300 neuroblastoma, like human neuroblastoma, elicits an immune response in its host and as a result provides an animal model in which to study the enigmatic behavior of this common childhood tumor. Since the liver is a favored site for neuroblastoma metastasis, especially the favorably regressing IV-S stage, and since the liver is a known producer of immunoregulatory factors, this study report a systematic assessment of liver cell tumor cell interaction, the effect on tumor immunogenicity, and the potential for tumor growth control. Immunization-excision-challenge assays in 120 A/J mice with C1300 demonstrate the tumor to be antigenic; but in a second experimental sequence with 120 mice, normal whole liver cells were admixed with C1300 tumor cells in vitro and incubated for one hour prior to animal innoculation. The immunogenicity is dramatically minimized in the admixture group when compared with controls (antigenic ratio = 1.67 versus 3.07, p less than .02). However, if prior to such liver cell-tumor cell admixture the liver cells are sonicated and the lysate ultracentrifuged, a contrasting result is obtained. In 4 additional experiments utilizing 120 mice, the tumor cell is rendered a more potent immunogen following soluble fraction admixture (antigenic ratio = 1.99 versus 1.56, p less than .05). These data suggest that such whole cell and subcellular soluble factor immunoregulatory interactions are operative in determining immunogenicity of a tumor innoculation. We speculate that the progression or regression of clinical neuroblastoma within the liver may be similarly influenced since a host-tumor interaction depends on eliciting an antitumor response to an antigenic stimulus.