Prognostic significance of changes in IL-12 secretion during cancer immunotherapy with IL-2: Preliminary considerations

IL-2 cancer immunotherapy has been proven to stimulate the release of most cytokines, including IL-6, IL-10, IL-1 and IL-5, however al present, there are no data concerning the effect of IL-2 on the secretion of the other main antitumor cytokine, IL-12. This preliminary clinical study was performed to evaluate changes in IL-12 blood levels during IL-2 immunotherapy, and their eventual relation with the clinical response. The study included 13 metastatic renal cell cancer patients able to be evaluated who were undergoing SC low-dose IL-2 immunotherapy, consisting of 6000,000 IU/day for 6 days/week for 4 weeks. The clinical response was partial response (PR) in 3, stable disease (SD) in 5 and progressive disease (PD) in the last 5 patients. Mean serum levels of IL-12 significantly increased on IL-2 therapy Moreover IL-12 mean levels observed during IL-2 injections in patients with response or SD were significantly higher than in those who progressed. in addition, IL-6 increase was significantly lower in patients with IL-2-induced increase in IL-12 levels greater than 100% than in patients with no rise or an increase lower than 100%. The same behavior was observed for IL-10, even though the difference was not significant. in contrast, no difference was seen in Neopterin mean levels on treatment. Finally, lymphocyte increase was significantly higher in patients with evident increase in IL-12 in response to IL-2. This pilot study shows that IL-2 in vivo may stimulate the macrophagic release of IL-12, and suggests that IL-2-induced IL-12 increase may have favorable prognostic significance, being associated with an apparent increased efficacy of IL-2 cancer immunotherapy.