title: Accelerated rejection of the second transplants of immunogenic tumor in mice under inhibition of indoleamine 2,3-dioxygenase activity by ethyl pyruvate.
abstract: OBJECTIVE
  A recently discovered enzyme, indoleamine 2,3-dioxygenase (IDO), is expressed in placenta, dendritic cells and also in many kinds of tumors and in tumor-infiltrating macrophages. By catabolizing tryptophan, IDO causes local depletion of this essential amino acid and excess of kinurenin, and suppresses in situ proliferation and functioning of T lymphocytes. Thus, immune resistance of tumors can be overcome by inhibiting IDO activity.
  
  
  METHODS
  C3HA mice immunized with non-syngeneic H-29 tumor were used to study the effect of the IDO inhibitor ethyl pyruvate, under systemic or local (at site of tumor cells localization) administration, on the occurrence and rate of rejection of the second transplants of this tumor.
  
  
  RESULTS
  Both systemic and local administration of ethyl pyruvate increases the incidence of and substantially accelerates tumor regression as compared with control.
  
  
  CONCLUSIONS
  IDO inhibitors impairing immune resistance of tumors may appear useful in leveraging the efficacy of antitumor therapy.
authors.affiliation: Institute of Cytology and Genetics of Siberian Department of the Russian Academy of Sciences, Novosibirsk 630090, Russian Federation.
authors.forename: E D
authors.initials: ED
authors.lastname: Vasilyeva
authors.forename: V
authors.initials: V
authors.lastname: Kaledin
authors.forename: V P
authors.initials: VP
authors.lastname: Nikolin
authors.forename: N A
authors.initials: NA
authors.lastname: Popova
authors.forename: I A
authors.initials: IA
authors.lastname: Kirilyuk
authors.forename: I A
authors.initials: IA
authors.lastname: Grigor'ev
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006084:Graft Rejection; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D011773:Pyruvates / Q000008:administration & dosage / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011773:Pyruvates; C046522:ethyl pyruvate