Immune-mediated regression of 'metastatic' neuroblastoma in the liver.
It is understood that neuroblastoma (NB) in the liver of patients with clinical stage IV-S disease may disappear, but the mechanism of such regression is unclear. A genetic hypothesis has previously been suggested, although heretofore an immunologic explanation had not been reported. Using C1300 NB in AJ mice, we developed a model of liver metastatic disease by directly injecting tumor cells into a subcutaneously translocated spleen. Intrasplenic inoculation of 2 x 10(6) C1300 NB cells produced liver subcapsular foci of NB in 100% of animals, whose mean survival period was 18 days. Three days after tumor inoculation, interleukin-2 (IL-2) (2,400 U/d) was continuously infused for 14 days via a miniosmotic pump, and daily survival was followed. Animals were sampled serially by histological and immunohistochemical staining. Animal survival was significantly prolonged (P < .05) in the IL-2 group when compared with that of saline controls, but importantly, 50% of the mice were cured. Histological examination showed early infiltration of mononuclear cells, predominantly lymphocytes, around liver metastatic foci; and phenotypic analysis of these cells showed them to be Thy-1.2-positive and asialo GM1-positive, suggesting they are of natural killer (NK) and lymphokine-activated killer (LAK) origin. Most importantly, in cured animals the histological analysis of the liver demonstrated reversion to a scar-free anatomy, akin to that seen in stage IV-S NB survival. These data suggest that immune-mediated regression of NB in the liver is possible; whether the result of therapy or spontaneous, the liver histology reverts to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishizu
H
H
Division of Pediatric Surgery, Children's Hospital Medical Center, Cincinnati, OH 45229-2899.
Bove
K E
KE
Ziegler
M M
MM
Arya
G
G
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D012074:Remission Induction; D012075:Remission, Spontaneous
D007376:Interleukin-2