title: Therapy implications of the role of interleukin-2 in cancer.
abstract: Despite its apparent failure in cancer therapy, IL-2 still remains fundamental in the activation of antitumor immunity. Areas covered: The aim of this review is the reinterpretation of the role of IL-2 in anticancer immunity, according to knowledge gained of the cytokine network, by highlighting its importance in inducing T helper-1 (TH1) cell proliferation, natural killer (NK) actHivation and IL-12 secretion. However, its main negative effect is the stimulation of regulatory T cells (Tregs), which in contrast suppresses anticancer immunity. Expert commentary: Cardiovascular toxicity, which was the main clinical problem at the beginning of IL-2 therapy at high intravenous doses, has almost been completely solved by subcutaneous low-dose IL-2 injection. In order to enhance the anticancer efficacy of IL-2, several strategies have been explored, including chemotherapy and interferon, but up until now no regimen has appeared to be clearly better than IL-2 alone. However, considering the role of immune checkpoints (PD-1 and CTLA-4) in Tregs stimulation, the most effective immunotherapy in the future could be concomitant IL-2 administration, to enhance lymphocyte count, and checkpoint inhibitors, such as anti-PD1 or anti-CTLA-4 monoclonal antibodies, or IL-12, which is also able to counteract IL-2-induced Treg cell generation. Therefore, the time for IL-2 immunotherapy in cancer treatment has finally arrived.
authors: a Department of Oncological Service , Institute of Biological Medicine , Milan , Italy.
authors: Paolo
authors: P
authors: Lissoni
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000276:immunology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D049109:Cell Proliferation; D004359:Drug Therapy, Combination; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D007376:Interleukin-2; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D018664:Interleukin-12
keywords: Cancer immunotherapy; IL-12; IL-2 immunotherapy; checkpoint inhibitors; cytokines