Dose and timing of total-body irradiation mediate tumor progression and immunomodulation

The major goal of this study was to examine the effects of total-body irradiation (TBI) on lung carcinoma progression and determine if changes in tumor growth could be correlated with radiation-induced alterations of immune system parameters. Lewis lung tumor cells were injected subcutaneously into syngeneic C57BL/6 mice that had been irradiated with a single 3.0 Gy dose of gamma-rays (60Co) at four time points either before or after tumor cell implantation. Subsequently, a second group of mice was irradiated 2 h prior to tumor injection with sequential doses of gamma-rays (0.46-2.66 Gy range). Assays were performed on blood and spleen from mice euthanized 16 days postimplantation. Tumor growth was consistently slower regardless of the timing of radiation exposure. However, dose of radiation influenced tumor growth delay. The preirradiated tumor-bearing mice had high CD4/CD8 T lymphocyte ratios along with increasing percentages of NKT cells in the blood supply with dose. Tumor-induced immunomodulation was also present, as evidenced by splenomegaly, low proliferative response to mitogens, and decreased spontaneous blastogenesis of leukocytes within the blood compared with normal values (P < or = 0.01). Anemia and thrombocytopenia were not observed with either tumor presence or irradiation. The present study demonstrates that a modest dose of TBI prior to tumor cell implantation resulted in a beneficial antitumor effect. A selective radiation-induced depletion of CD8+ T lymphocytes and changes in NKT cell percentages, correlated with findings from cytotoxicity assays, were indicative of a protumoricidal immune environment.