Increased immunogenicity of murine lymphoma cells following exposure to gamma rays in vivo.

Studies performed in our laboratory showed that a marked increase in immunogenicity occurred in murine lymphoma cells exposed to a mutagenic compound such as 5 (3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC in vivo or in vitro. Subsequently, further experiments were conducted to test whether ionizing radiations would be able to affect the immunogenic properties of cancer cells in a mouse leukemia model. Male CD2F1 mice were inoculated with histocompatible L1210 Ha leukemia and treated with 400 R of total-body irradiation. A number of transplant generations were carried out with leukemic cells collected from irradiated donors, thus generating a "radiation treated line" (RTL). The immunogenicity of RTL cells increased significantly with respect to that of L1210 Ha line as early as 3 passages in vivo. However, no strong transplantation antigens comparable to those elicited by treatment with DTIC were found in RTL cells, even after a number of transplant generations. Combined effects of bis-chloroethyl-nitrosourea and weak anti-RTL responses of the host were markedly synergistic. Moreover, RTL lymphoma acquired strong immunogenic properties after a single cycle of DTIC treatment in vivo. These results may provide a model for exploiting radiation-induced increase of tumor cell immunogenicity for combined radio-immunochemotherapy.