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Maintenance and Cure of the L5178Y Murine Tumor-dormant State by Interleukin 2: Dependence of Interleukin 2 on Induced Interferon- and on Tumor Necrosis Factor for Its Antitumor Effects¹

Department of Pathology and Laboratory Medicine, Hahnemann University, Philadelphia, Pennsylvania 19102

We reported previously that treatment of peritoneal cell (PC) cultures prepared from mice which harbor L5178Y lymphoma cells in a tumordormant state in their peritoneal cavity with interleukin 2 (HuIL-2) stimulated antitumor cytotoxic activity in both the nonadherent and adherent populations derived from such cultures. We report here that HuIL-2 induced the production of murine interferon (MuIFN-) in these PC cultures and required Lyt-1-, Lyt-2-, and L3T4-expressing lymphocytes to do so. HuIL-2 required and synergized with this induced MuIFN- to stimulate cytotoxic activity in the nonadherent PC and the MuIFN- itself stimulated cytotoxic activity in the adherent PC. Cyclosporin A prevented both the induction of MuIFN- and the development of antitumor cytotoxic activity in HuIL-2-treated PC cultures. An add-back of exogenous MuIFN- to HuIL-2-cyclosporin A-treated PC cultures and to the nonadherent subpopulation of such cultures, at a concentration which itself produced no antitumor effect, permitted HuIL-2 to induce its antitumor effect. We previously reported that MuIFN- requires the action of murine tumor necrosis factor (MuTNF) to induce cytotoxic activity in PC cultures from tumor-dormant mice. We report here that HuIL-2 also requires the action of (MuTNF) to stimulate antitumor cytotoxic activity in PC cultures from tumor-dormant mice. These results indicate that HuIL-2 induces MuIFN- and requires and synergizes with this MuIFN- and with (MuTNF) to stimulate antitumor cytotoxic activity in PC cultures from tumor-dormant mice.

¹ Supported by PHS Grant CA32577, awarded by the National Cancer Institute, HHHS, and by a grant from Hoffmann La Roche.

² Current address: Second Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.

³ Current address: Beckman Instruments, 200 S. Kraemer Blvd., Brea, CA 92621.

⁴ To whom requests for reprints should be addressed, at Department of Pathology, Hahnemann University, Broad and Vine Streets, Philadelphia, PA 19102.

Received 9/ 7/88. Revised 7/13/89. Accepted 11/27/89.