title: Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy.
abstract: Interleukin-2 (IL-2) is a cytokine with pleiotropic effects on the immune system. Systemic IL-2 treatment has produced durable responses in melanoma and renal cancer patients, but unfortunately this is effective only in a fraction of patients. Moreover, IL-2 treatment also engenders serious side effects, which limit its clinical utility. It is now appreciated that IL-2 not only stimulates NK and effector T cells but also has a critical role in the generation and maintenance of regulatory T cells, which act to dampen immune responses. Thus, successful immunotherapy of cancers using IL-2 has to address two fundamentally important issues: (1) how to limit side effects yet be active where it is needed, and (2) how to preferentially activate effector T cells while limiting the stimulation of Tregs. Strategies are now being developed to address these critical obstacles that may lead to a renaissance of IL-2 therapy.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY14642, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Skrombolas
authors.forename: John G
authors.initials: JG
authors.lastname: Frelinger
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D007376:Interleukin-2; D015375:Receptors, Interleukin-2