title: Strategies to reverse melanoma-induced T-cell dysfunction.
abstract: Patients with advanced melanoma can develop spontaneous cellular and humoral responses to tumor antigens. Understanding the failure of spontaneous or vaccine-induced tumor antigen-specific T-cell responses to promote the immunologic clearance of melanomas is critical. Multiple mechanisms of melanoma-induced immune escape, which are likely to cause the failure of the spontaneous or vaccine-induced immune responses to promote tumor regression in humans, have been elucidated. In addition, a number of negative factors in the tumor microenvironment dampen antitumor immune responses, including cytokines (like transforming growth factor-β or interleukin-10), suppressive cells (regulatory T cells and myelosuppressive dendritic cells), defective antigen presentation by tumor cells (human leukocyte antigen or T antigen expression loss, antigen processing machinery defects), amino acid catabolizing enzymes (indoleamine-2-3 dioxygenase, arginase), and immune inhibitory pathways (like cytotoxic T-lymphocyte antigen 4/cluster of differentiation 28, programmed death 1/programmed death 1 ligand 1). This information has been used to develop a number of therapies to specifically target these negative regulators of antimelanoma immune responses to enhance tumor antigen-specific immune responses and to increase the likelihood of clinical benefits in patients with advanced melanoma.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Fourcade
authors.forename: Hassane M
authors.initials: HM
authors.lastname: Zarour
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines