Immunosuppressive and immunostimulatory factors produced by malignant cells In vitro

The addition of small numbers of irradiated mouse fibrosarcoma cells to cultures containing syngeneic mouse spleen cells and sheep erythrocytes resulted in almost complete inhibition of the expected anti‐sheep hemolytic plaque‐forming cell responses; the addition of even smaller numbers resulted in stimulation rather than inhibition. This same pattern was reproduced when various other types of syngeneic or allogeneic malignant cells were tested under similar conditions; the presence of strong (H‐2) histocompatibility differences had no apparent effect. Metabolically active irradiated malignant cells were required to produce inhibition; dying cells or soluble extracts of cells were ineffective. However, serum‐free supernatants from healthy cultures of non‐irradiated fibrosarcoma cells were found to be inhibitory at high concentrations and stimulatory at low concentrations, in a pattern similar to that found when intact irradiated fibrosarcoma cells were used. High‐speed centrifugation of such supernatants sedimented the stimulatory material but left the inhibitory material in solution. When syngeneic fetal fibroblasts were substituted for the fibrosarcoma cells, it was found that both the intact fibroblasts and their culture supernatants were stimulatory, and that the stimulatory material could be sedimented as before by high‐speed centrifugation. However, very little inhibitory effect was produced by either intact fibroblasts or their culture supernatants, except when unusually high concentrations were used. It is concluded that at least some types of healthy malignant cells release soluble material capable of inhibiting immune responses: their non‐malignant counterparts produce little if any inhibitor.