Gene expression signatures of interleukin-2 in vivo and in vitro and their relation to anticancer therapy

Treatment with human recombinant interleukin-2 (rIL-2) can successfully eradicate advanced cancer in humans; however, its utilization is limited by the unpredictability of its effectiveness and the excessive toxicity often associated with its use. The mechanisms responsible for immune-mediated tumor regression and those associated with limiting toxicity have not yet been sorted out. Thus, this review critically addresses what has been done in the past to understand this biologically and practically important question and discusses future strategies to enhance the understanding of this interesting model of immune-mediated tumor rejection. In particular, the first aim of this review is to discuss what is known about the mechanism(s) responsible for tumor rejection; the second aim is to review the relationship between the toxicity induced by rIL-2 treatment and its effectiveness; the third aim is to summarize novel insights into the possible mechanism of rIL-2 activity in vivo using high-throughput strategies aimed at the global assessment in real-time of events associated with rIL-2 therapy in humans. This information will not only lead to a better utilization of this biological agent in clinical practice but it may also provide important information about how immune-mediated tissue rejection occurs.