Interleukin-2 activated cytoxic lymphocytes (LAK cells) as antigen nonspecific amplifiers of the immune response: General characteristics and considerations for cancer therapy

C. Presence of Tumor During Activation Can Be Inhibitory Injection of IL-2 directly into tumor sites has been shown in animal models to be successful to reducingtmor and resulting in a state of To determine whether LAK could be generated in such a milieu, we tested the effects of tumor presence on LAK activation as a function of IL-2 concentration. Table 1 indicates that with either cultured glioma or fresh human sarcoma tumors, LAK activation was considerably suppressed. Many human tumors are known to secrete immunosuppressive factors, which can inhibit LAK activation.35-37 Even at 500 units per m4 of IL-2, we were unable to generate optimal LAK at a 100 to 1 lymphocyte to tumor ratio with either type of tumor cell included in the culture. If LAK activation in vivo at the tumor site is to be considered as a therapeutic option, then the lymphocytes and IL-2 must be available in excessive quantities in relation to the number of tumor cells, or tumors must not be as immunosuppressive as those we tested. However, once activated, these LAK can be maintained in the presence of activation-suppressive tumor cells at very high tumor to LAK ratios as reported prev iouly. D. LAK Activation is Inhibited by Hydrocortisone, but Not Cyclosporine Because we have been successful in activating patients’ PBL even after extensive chem- otherapy, it was of interest to us to define what effect known immunosuppressive drugs would cause. Our recent results showed that LAK activation is exquisitely sensitive to hydrocortisone, even at doses that have little or no effect on CTL activation (10-5 to 10-6 M).38 Interestingly, cyclosporine A (CsA, Sandoz Pharmaceuticals) had no effect on LAK activation but totally prevented the activation of CTL (Figure 3).