Regulation of B-cell lymphoma growth in syngeneic SJL/J mice. establishment of tumor dormancy following administration of anti-CD4 monoclonal antibody into tumor-bearing mice.
The spontaneously arising B-cell lymphoma (la+ reticulum cell sarcoma, RCS) in SJL/J mice has been shown to depend on host CD4 T cells for proliferation and growth. Treatment of mice with CD4 monoclonal antibody (mAb) prior to or after inoculation of a lethal dose of RCS tumor cells inhibits cell growth and the mice survive. The mechanism of tumor growth inhibition was studied by adoptively transferring cells from CD4 mAb treated tumor bearers into naive syngeneic mice. The recipient mice developed tumors and died. Tumor growth was dependent on the concentration of the adoptively transferred tumor cells. These results suggested that a state of tumor dormancy was established in the treated mice. Tumor dormancy was long lasting, as cells transferred as late as 11 weeks after the initial RCS inoculation still developed tumors in the recipient. The maintenance of dormancy was not due to failure of the recipient mice to mount an anti-tumor response or to the induction of suppressor cells. These results suggest that in the absence of CD4 cells, the RCS tumor remains dormant and this state of dormancy persists for long periods after total recovery of the CD4 cell subpopulation. Thus, it appears that RCS proliferation and growth is dependent on host CD4 cells but maintenance is under the influence of other cells or factors. Further characterization of this tumor dormant system and its regulation by the host may reveal novel mechanisms of tumor dormancy.
Ohnishi
K
K
Internal Medicine III, Hamamatsu University School of Medicine, Japan.
Bonavida
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D016393:Lymphoma, B-Cell / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D014185:Transplantation, Isogeneic
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens