IMMUNE MODULATION BY INTERLEUKIN-12 IN TUMOR-BEARING MICE RECEIVING VITAMIN-D-3 TREATMENTS TO BLOCK INDUCTION OF IMMUNOSUPPRESSIVE GRANULOCYTE MACROPHAGE PROGENITOR CELLS/

Lewis lung carcinoma (LLC-LN7) tumors stimulate myelopoiesis and incre ase the presence of granulocyte/macrophage (GM) progenitor cells havin g natural suppressor activity. Treatment of these tumor-bearing mice w ith interleukin-12 (IL-12) resulted in minimal immune modulation. The objective of this study was to determine whether eliminating natural s uppressor activity would allow for immune stimulation by IL-12. Treatm ent of LLC-LN7 tumor-bearing mice with vitamin D-3 eliminated natural suppressor activity. In mice that were first treated with vitamin D-3 and then also with IL-12, there was stimulation of splenic T cell prol iferation in response to immobilized anti-CD3 plus IL-2. In addition, spleen and lymph node cells from vitamin-D-3/IL-12-treated tumor-beari ng mice became stimulated in response to autologous tumor to produce i nterferon gamma (IFN gamma), although IL-2 production was not stimulat ed. A prominent effect of the combined vitamin-D-3/IL-12 treatment reg imen was the synergistic augmentation of autologous tumor-specific cyt olytic activity within the regional lymph nodes. The generation of the se tumor-specific effector cells required the presence of the tumor ma ss since such activity was not elicited in the lymph nodes of mice fro m which the tumors had been surgically excised. The results of this st udy show that, after treatment of tumor bearers with vitamin D-3 to el iminate GM-suppressor cells, IL-12 can induce select regional antitumo r immune responses, particularly IFN gamma production and cytolysis by regional lymph node cells of autologous tumor.