The Prostate 70:1461^1470 (2010) Indoleamine 2,3 -Dioxygenase (IDO) Activity InfluenceTumor Growth in theTRAMP Prostate Cancer Model Eva Ka ¨llberg, 1 * Pernilla Wikstro ¨m, 2 Anders Bergh, 2 Fredrik Ivars, 1 and Tomas Leanderson 1 1 Immunology Group, Lund University, Lund, Sweden 2 Department of medical bioscience,UmeÔ University,UmeÔ, Sweden 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 þ and CD31 À cells. Essentially no CD45 þ , 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 À/À animals and J-chain negative (J À/À ) mice that have perturbed IDO activity. In both crosses a delayed tumor incidence was observed. CONCLUSION. 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 À/À mice was indistinguishable from that of C57BL/6 animals the IDO expression in the tumor tissue appears to be irrelevant for TRAMP tumor incidence. Prostate 70: 1461 – 1470, 2010. # 2010 Wiley-Liss, Inc. KEY WORDS: TRAMP; IDO; immunology INTRODUCTION Prostate cancer is a common disease and affects over 200,000 men in the U.S. alone each year. Some prostate tumors do not grow whereas others rapidly produce metastases [1]. At this stage of disease only palliative treatment in the form of castration is available. In addition, such tumors generally undergo transition into a castration-resistant phenotype and eventually kill the patient. The transition into a more aggressive disease most likely involves other events than the reduced need for circulating testosterone. Hence, while the immune system is capable of detecting and killing tumor cells [2], so called immune surveillance, this function appears to be down-regulated in tumor bearing individuals. The regulation of this immune suppres- sion exerted by solid tumors is complex. Recently a Grant sponsor: Swedish Cancer Foundation; Grant sponsor: Swedish Research Council. *Correspondence to: Eva Ka ¨llberg, Immunology Group, Lund University, Lund, Sweden. E-mail: eva.kallberg@med.lu.se Received 27 January 2010; Accepted 23 March 2010 DOI 10.1002/pros.21181 Published online 4 May 2010 in Wiley Online Library (wileyonlinelibrary.com). ß 2010 Wiley-Liss, Inc.