title: Indoleamine 2,3-dioxygenase (IDO) activity influence tumor growth in the TRAMP prostate cancer model.
abstract: BACKGROUND
  Indoleamine 2,3-dioxygenase (IDO) activity has been shown to be expressed in local lymph nodes and induce immune suppression of tumor immunity. Here we analyze the effect of IDO expression on prostate tumor growth using the transgenic adenocarcinoma of mouse prostate (TRAMP) animal model.
  
  
  METHODS
  Mice deficient in IDO expression were crossed to TRAMP mice and the time to the appearance of palpable tumors were measured. Immune histology was used to analyze the IDO expressing cells in tumors and in local lymph nodes. The levels of the substrate for IDO (tryptophane) and its product (kynurenine) was measured by HPLC.
  
  
  RESULTS
  We found that systemic IDO activity, determined as the kynurenine/tryptophan ratio in serum, correlated with the presence of palpable tumor. Immunohistological analysis showed increased numbers of IDO expressing cells in local lymph nodes. In tumors, IDO expression could be detected in the tumor stroma by both CD31+ and CD31(-) cells. Essentially no CD45+, IDO expressing cells could be detected in the tumors. The influence of IDO activity on tumor progression was analyzed by back-crossing TRAMP mice with IDO(-/-) animals and J-chain negative (J(-/-)) mice that have perturbed IDO activity. In both crosses a delayed tumor incidence was observed.
  
  
  CONCLUSIONS
  Our results argue for a role for IDO mediated immune suppression in the early stages of prostate cancer progression. However, since the intra-tumor IDO expression in J(-/-) mice was indistinguishable from that of C57BL/6 animals the IDO expression in the tumor tissue appears to be irrelevant for TRAMP tumor incidence.
authors.affiliation: Immunology Group, Lund University, Lund, Sweden. eva.kallberg@med.lu.se
authors.forename: Eva
authors.initials: E
authors.lastname: Källberg
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wikström
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ivars
authors.forename: Tomas
authors.initials: T
authors.lastname: Leanderson
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D018450:Disease Progression; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014364:Tryptophan / Q000097:blood
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan