The effect of the immune status of the TAR mouse on the growth and metastasis of tumour xenografts

Abstract

Mice thymectomised at 3–4 weeks of age and subsequently given whole-body irradiation ( 9 Gy) under cytosine arabinoside cover (TAR mice) provide an alternative model to the athymic nude (nu+/nu+) mouse for studying the biological characteristics of tumour xenografts. In the present study we have evaluated the repopulation events in the bone marrow and spleen following whole body irradiation of TAR mice, and analysed immune competence up to 98 days following irradiation. Repopulation of both bone marrow and spleen was evident in the weeks following whole body irradiation, and an initial increase in the relative proportion of T-lymphocytes present in the spleen was followed by a decrease in the percentage of lymphocytes expressing T-cell markers, which remained below the level observed in control mouse spleen cell preparations. TAR mice exhibited a decreased ability to respond to a non-specific T-cell mitogen and to elicit a T-cell dependent antibody response to influenza viral antigen. Both TAR and control mice possessed macrophages which could be activated to the tumouricidal state, and natural killer activity of TAR mice was enhanced greater than 3-fold above control values. The ability of TAR mice to accept tumor xenografts decreased with the increasing time interval between irradiation and subcutaneous implantation of tumour cells, and (in some instances) spontaneous regression was observed. In addition, a hamster tumour cell line possessing high metastatic potential in its syngeneic host was shown to metastasise to the regional lymph node, lungs, liver, kidneys and spleen of TAR mice from a cell inoculum implanted subcutaneously immediately after irradiation; however, with increasing time between irradiation and inoculation of tumour cells tumour metastasis decreased. The ability of TAR mice to support the growth and metastasis of tumour xenografts would appear to inversely correlate with the increase in natural killer cell activity following irradiation.