M M Ziegler1, H Ishizu, E Nagabuchi, N Takada, G Arya. 1. Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, USA.
Abstract
BACKGROUND: The prognosis for children with neuroblastoma (NB) remains dismal, in part because of extent of disease at diagnosis as well as resistance of tumors to conventional therapies. However, human NB exhibits many favorable traits, including the capability to mature into a more benign form or to regress spontaneously. A murine model of disease that could permit eventual genetic manipulation, so that such beneficial traits could be identified or even augmented, would be most useful. METHODS: This report details an analysis of the contemporary study of the tumor growth, metastases, immunogenicity, and immunotherapy of murine NB and compares it with known patterns of clinical NB. RESULTS: Striking similarities exist in the local tumor growth and metastatic behaviors of murine and human NB, behaviors that in part may be related to a host-tumor immunologic response. The naturally low expression of class I antigen in NB, the ability to augment that expression with cytokines, and the phenotype of the cellular and humoral immune response to NB are strikingly similar in human and murine hosts. Comparable immunotherapeutic potential exists. There have been rare and sporadic observations of spontaneous regression of an existing murine NB, unlike the more predictable regression of Evans Stage IV-S clinical NB. CONCLUSIONS: The many similar biologic, physiologic, and immunologic characteristics of human and murine NB make the murine model a valuable adjunctive aid in furthering our understanding of human disease.
BACKGROUND: The prognosis for children with neuroblastoma (NB) remains dismal, in part because of extent of disease at diagnosis as well as resistance of tumors to conventional therapies. However, human NB exhibits many favorable traits, including the capability to mature into a more benign form or to regress spontaneously. A murine model of disease that could permit eventual genetic manipulation, so that such beneficial traits could be identified or even augmented, would be most useful. METHODS: This report details an analysis of the contemporary study of the tumor growth, metastases, immunogenicity, and immunotherapy of murine NB and compares it with known patterns of clinical NB. RESULTS: Striking similarities exist in the local tumor growth and metastatic behaviors of murine and human NB, behaviors that in part may be related to a host-tumor immunologic response. The naturally low expression of class I antigen in NB, the ability to augment that expression with cytokines, and the phenotype of the cellular and humoral immune response to NB are strikingly similar in human and murine hosts. Comparable immunotherapeutic potential exists. There have been rare and sporadic observations of spontaneous regression of an existing murine NB, unlike the more predictable regression of Evans Stage IV-S clinical NB. CONCLUSIONS: The many similar biologic, physiologic, and immunologic characteristics of human and murine NB make the murine model a valuable adjunctive aid in furthering our understanding of human disease.