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 conta ining interleukin-2 (IL-2) cDNA and selected in G418. Parental tumor c ells and those that produced IL-2 were injected in vivo. Whereas injec tion of parental tumor cells resulted in progressive tumor growth, tho se secreting high levels of IL-2 were rejected. Furthermore, the immun osuppression associated with inoculation of parental tumor cells was n ot seen. To understand the failure of mice to reject non-IL-2-secretin g tumor cells, functional responses of spleen cells from immune and tu mor-bearing mice were studied in vitro. As expected, immune spleen cel ls proliferated under a variety of conditions but were inhibited in th e presence of parental tumor cells. Even spleen cells from tumor-beari ng animals responded well in the absence of parental tumor cells or in the presence of parental tumor cells, if supplied with adequate level s of IL-2. These results suggest that both tumor-bearing and immune mi ce generate antitumor effectors but that the cells might be functional ly suppressed because of their inability to secrete IL-2 after contact with parental tumor cells.