title: Update on the role of ipilimumab in melanoma and first data on new combination therapies.
abstract: OBJECTIVE
  This article provides an update on the therapeutic role of the monoclonal antibody ipilimumab in melanoma. Recent therapeutic combinations, as well as directions for further investigations, will also be discussed.
  
  
  RESULTS
  By blocking the interaction between CTLA-4 and B7 expressed on activated T lymphocytes and antigen-presenting cells, respectively, ipilimumab inhibits negative signals that physiologically downregulate T-cell activation and exerts its therapeutic activity by upregulating the antitumor activity of T lymphocytes. Ipilimumab has been the first agent to significantly improve the survival of metastatic melanoma patients and to provide long-term benefit to a sizeable proportion of patients treated within phase II/III studies and expanded access programs. On these premises, a number of studies combining ipilimumab with cytotoxic, antiangiogenic, and targeted agents have been most recently conducted.
  
  
  CONCLUSIONS
  Ipilimumab is the prototype of a growing family of 'immunomodulating antibodies' and it has demonstrated that immunotherapy will play an increasingly important role in the new treatment approaches for cancer. Combinations of chemotherapy, radiation therapy, and targeted drugs with ipilimumab indicate that additive and synergistic antitumor activity can be achieved. Most importantly, they indicate that involving the immune system is a key strategy to improve the outcome in cancer patients.
authors.affiliation: Medical Oncology and Immunotherapy, Azienda Ospedaliera Universitaria Senese, Istituto Toscano Tumori, Siena, Italy. mmaio@cro.it
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Anna M
authors.initials: AM
authors.lastname: Di Giacomo
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy*; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D000074324:Ipilimumab