Optimising IL-2 for Cancer Immunotherapy

The key role of T cells in cancer immunotherapy is well established and is highlighted by the remarkable capacity of Ab-mediated checkpoint blockade to overcome T -cell exhaustion and amplify anti -tumor responses. However, total or partial tumor remission following checkpoint blockade is still limited to only a few types of tumors. Hence, concerted attempts are being made to devise new methods for improving tumor immunity. Currently, much attention is being focused on therapy with IL -2. This cytokine is a powerful growth factor for T cells and optimises their effector functions. When used at therapeutic doses for cancer treatment, however, IL -2 is highly toxic. Nevertheless, recent work has shown that modifying the structure or presentation of IL -2 can reduce toxicity and lead to effective anti -tumor responses in synergy with checkpoint blockade. Here, we review the complex interaction of IL -2 with T cells: first during normal homeostasis, then during responses to pathogens, and finally in anti -tumor responses.