EFFECT OF INTERLEUKIN-12 IMMUNOTHERAPY ON ENDOGENOUS SECRETION OF INTERLEUKIN-2 IN METASTATIC CANCER-PATIENTS

The interactions between the antitumor cytokines interleukin (IL)-2 an d IL-12 play a fundamental role in the physiopathology of anticancer i mmunity In vitro, IL-2 has no stimulatory effect on IL-12 production. In contrast, IL-2 has been proved to induce IL-12 secretion in vivo, a nd IL-2-induced IL-12 production is associated with the clinical effic acy of IL-2 anticancer immunotherapy. On the other hand, IL-12 may sti mulate the in vitro secretion of IL-2, whereas at present there are no data in vivo. This preliminary study was performed to evaluate IL-2 s ecretion in cancer patients treated with IL-12 immunotherapy. The stud y was carried out in metastatic renal cancer patients. Each cycle of I L-12 consisted of one subcutaneous injection at 1.25 mcg/kg/body weigh t once a week for 3 consecutive weeks. Six IL-12 cycles were evaluated , by collecting blood samples before and after each IL-12 injection. N o significant changes in mean serum levels of IL-2 were observed durin g IL-12 immunotherapy. Therefore, this preliminary study would suggest that IL-12 is unable to stimulate the secretion of IL-2 in vivo, desp ite its well-documented stimulatory action in vitro. In conclusion, th ese data, taken together with those showing a stimulatory effect of IL -2 on IL-12 secretion in vivo, would suggest that IL-12 immunotherapy is biologically less effective with respect to that of IL-2, because o f its lack of capacity to induce a concomitant secretion of IL-2.