title: Overcoming immune resistance in the tumor microenvironment by blockade of indoleamine 2,3-dioxygenase and programmed death ligand 1.
abstract: The specificity of antitumor immunity continues to attract interest as a potentially powerful mode of cancer treatment. Cancer vaccines and adoptive T-cell infusion are strategies that can increase the frequency of circulating tumor antigen-specific T-cells. However, although these approaches can produce clinical responses in a minority of patients, tumor escape from immune destruction appears to dominate in many instances. Several molecular mediators of tumor resistance to immune effector cells have been identified that can be targeted pharmacologically. Two of these, the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase and the T-cell inhibitory programmed death ligand 1, are discussed in this review. Blockade of these molecules may increase the efficacy of tumor-specific T-cell therapies in cancer patients.
authors.affiliation: Department of Pathology, Section of Hematology/Oncology, The University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA. tgajewsk@medicine.bsd.uchicago.edu
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007113:Immunity, Innate; D061026:Programmed Cell Death 1 Receptor; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D014366:Tryptophan Oxygenase