The Effect of Bearing Tumours on the Ability of Mice to Reject Bone Marrow Transplants

To examine the possible relationship between the cells mediating resistance to tumour cells and those mediating rejection of foreign bone marrow transplants (BMT), the effect of tumour-bearing on BMT rejection has been measured by means of the spleen colony assay. Moderate doses (<5.0 × 10⁶) of bone marrow cells from DBA/2 strain mice, which normally produce few haemopoietic spleen colonies in γ-irradiated (950R) CBA/J strain mice, gave numerous (confluent) colonies when given soon after injection of Ehrlich ascites tumour (EAT) cells. Transfusion of [³H]UdR-labelled DBA/2 bone marrow cells demonstrated that the increased spleen colony formation in tumour-bearing mice was not due simply to changes in the total number of injected cells homing to the spleen. Injection of EAT ascites fluid alone, given to CBA/J mice before 950R+BMT, transiently reduced spleen colony development, the effect being more marked when fluid from older tumours was used. Supernatant fluid from EAT cells grown in vitro also depressed growth of BMT in vivo. The results reveal two processes in progress in mice bearing an ascites tumour: (1) an early reduction in the natural resistance to BMT allowing successful grafting and spleen colony formation, and (2) a progressive production by the tumour cells of short-acting soluble factors tending to suppress the proliferation of colony forming bone marrow cells in the transplant. The effect of the tumour-bearing state in weakening the natural resistance to foreign BMT strongly suggests that both tumour and foreign marrow graft resistance are mediated by the same or closely related effector cells.