An experimental model for evaluation of factors in tumor escape from immunological attack.

A model system is presented for studying the factors involved in tumor immunity. The initial observations with this system concern the importance of dose and route of administration of tumor cells on tumor growth. The data show that myeloma tumor cells, when inoculated i.v.in relatively large numbers, are eradicated by the immune response of an allogeneic host; tumor cells administered i.v. in smaller number escape from immune attack even though the host has the potential to mount an immune response. BALB/c mouse myeloma cells (MOPC-21) were transplanted s.c., i.p., or i.v. into H-2-compatible allogeneic DBA/ 2 mice. There was a marked difference in the response of the host to tumor given s.c. or i.p. as compared to tumor given i.v. Thus s.c. or i.p. inoculation resulted in lethal tumor growth when 5 x 10-3 or more tumor cells were given. In contrast, the outcome of i.v. inoculation depended on tumor cell dose. Although small cell doses ( 5x 10-4 down to 10-2) resulted in lethal tumor gosulted in lethal tumor growth with only 10% survival, large cell doses (10-5 to 5 x 10-7) resulted in tumor rejection and 70% survival. DBA/2 mice possess the immunological ability to react agaist the tumor when large doses of tumor cells (10-7) are given i.v. or i.p., since spleen cells obtained from such mice were found to be able to suppress the growth of MOPC-21 when a mixture of spleen cells and tumor cells was inoculated. On the basis of these initial observations, our model appears to relate especially to the idea that, in autochithonous tumor development or in metastasis of tumor, a small number of antigenic tumor cells, perhaps even a single cell, usually grows into a frank tumor in spite of the immunological competence od the host to respond to the tumor cells.