Maintenance and cure of the L5178Y murine tumor-dormant state by interleukin 2: in vivo and in vitro effects.

We studied the antitumor effects of recombinant human interleukin 2 (HuIL-2) in DBA/2 mice which harbor L5178Y lymphoma cells in a tumor-dormant state in the peritoneal cavity and in peritoneal cell (PC) cultures prepared from such mice. Intraperitoneal injection of 10,000 to 100,000 units of HuIL-2/day for 10 days eliminated tumor cells from 30-45% of the mice, whereas no mice became tumor-free in the phosphate-buffered saline-treated control group. In vitro, as little as 10 units/well HuIL-2 failed to stimulate cytotoxic activity in PC from normal mice. HuIL-2 directly stimulated antitumor cytotoxic activity in nonadherent but not in adherent PC cultures from tumor-dormant mice; however, treatment of whole PC from tumor-dormant mice with HuIL-2 resulted in the development of antitumor cytotoxic activity in the adherent PC population which were derived from such cultures. This suggests that the HuIL-2-treated nonadherent PC contributed to the cytotoxic activation of the adherent PC. Flow cytometric analysis of the PC from tumor-dormant mice revealed a polyclonal expansion of T-lymphocytes. Lyt-1+, Lyt-2+, and L3T4+ lymphocytes were all required for HuIL-2 to induce antitumor cytotoxic activity.