Effect of tumor irradiation on the uptake of lymphokine-activated killer cells in a murine tumor model.

Abstract

Immunotherapy with lymphokine-activated killer (LAK) cells and interleukin 2 is one of the newer treatment modalities for cancer. This raises important questions concerning synergism or suppressive effects of other existing treatment modalities on adoptive immunotherapy with LAK cells. A tumor model with H4IIe hepatoma cells grown on each flank of ACI rats was developed to evaluate the effect of external beam irradiation of tumors on the subsequent concentration of LAK cells in these tumors. Tumors on one side were irradiated at 6, 12, or 16 Gy prior to injection of [3H]thymidine-labeled LAK cells. The effect of irradiation was measured as the ratio of 3H recovered in the unirradiated tumor compared to that in the irradiated tumor in the same animal as a function of dose and time after irradiation. This ratio was significantly greater than 1.0 for a radiation dose of 12 Gy (2.35 +/- 0.51) measured 2 days after irradiation, indicating a reduction in LAK cell numbers in the irradiated tumor. This reduction in LAK cell number persists up to at least 4 days following radiation exposure. A similar experiment using 125I-labeled interleukin 2 showed equal distribution in the irradiated and unirradiated tumors. Our data demonstrates that the concentration of LAK cells is markedly reduced by prior radiation, in contradistinction to increased uptake of immunoglobulins in irradiated tumors, as shown by others. If a similar reduction is observed for longer duration after radiation exposure, it might suggest a clinically important interaction between prior radiation exposure and adoptive immunotherapy.