Indoleamine 2,3-dioxygenase (IDO) may not be a major factor for tumor immune evasion in multiple myeloma

Zojer, N., Schreder, M., Graffi, S., Fuchs, D., Sahota, S. and Ludwig, H. (2007) Indoleamine 2,3-dioxygenase (IDO) may not be a major factor for tumor immune evasion in multiple myeloma. Haematologica, 92 (Supp/2), PO-241.

Abstract

?Introduction. Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolising enzyme expressed by several cancers that induces immune tolerance. High IDO expression has been linked with short survival in some cancers, but data on the possible role of IDO are not available yet in multiple myeloma (MM).
Methods. We used quantitative (Q) PCR to evaluate IDO in CD138+ BM cells from MM patients (n=17), MM cell lines (n=6) and MM BM stromal cells (SCs) (n=5).
Results. Low level expression of IDO was found in the CD138+ BM fraction of 17 myeloma patients using Q-PCR (median 0.52 fold compared to normal PBMNC; range, 0.08-15.03). Even in the patient with highest IDO expression, IDO mRNA levels were >100x lower than in DCs or HeLa cells stimulated with IFN-g. Similarly, 6 myeloma cell lines had low IDO expression by qPCR (median 0.04; range 0.001- 0.68). Stimulation with IFN-g led to an upregulation of IDO in 2 of these cell lines, as shown by qPCR and Western blot, but again with expression levels being >100x lower than in activated DCs. Analysis of the tryptophan/kynurenin ratio in cell line culture supernatants furthermore revealed little sign of enzyme activity, even after stimulation. IDO expression could not be induced in the IDO- cell lines. Interestingly, when comparing CD138+ and CD138- cell fractions from BM of 3 myeloma patients, a detectable, although weak, PCR band was demonstrated in the CD138- fraction only. By conventional PCR using purified cell subsets from the CD138- fraction, a weak band was amplified from monocytes and T-cells. In cultured BM SCs from myeloma patients, IDO expression was low at baseline, but could be upregulated by interferon-g. IDO proved functional in this setting with reversal of the tryptophan/kynurenin ratio after 48 hours of interferon-g. BM-derived SCs from myeloma patients thus seem to have similar characteristics with regard to IDO expression as SCs from normal donors and do not appear to be a major source of IDO in myeloma when examined in isolation.
Conclusion. IDO is weakly expressed in myeloma plasma and stromal cells and may not contribute to immune paralysis in this disease.

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