Indoleamine 2,3-dioxygenase (IDO) activity influence tumor growth in the TRAMP prostate cancer model

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.

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.

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.

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.