TUMOR-BEARING ANIMALS CONTAIN SUPPRESSED ANTITUMOR EFFECTORS THE FUNCTION OF WHICH CAN BE UNMASKED BY IL-2

CMS5 fibrosarcoma cells were infected with retroviral constructs containing interleukin-2 (IL-2) cDNA and selected in G418. Parental tumor cells and those that produced IL-2 were injected in vivo. Whereas injection of parental tumor cells resulted in progressive tumor growth, those secreting high levels of IL-2 were rejected. Furthermore, the immunosuppression associated with inoculation of parental tumor cells was not seen. To understand the failure of mice to reject non-IL-2-secreting tumor cells, functional responses of spleen cells from immune and tumor-bearing mice were studied in vitro. As expected, immune spleen cells proliferated under a variety of conditions but were inhibited in the presence of parental tumor cells. Even spleen cells from tumor-bearing animals responded well in the absence of parental tumor cells or in the presence of parental tumor cells, if supplied with adequate levels of IL-2. These results suggest that both tumor-bearing and immune mice generate antitumor effectors but that the cells might be functionally suppressed because of their inability to secrete IL-2 after contact with parental tumor cells.