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

Indoleamine 2,3-dioxygenase (IDO) may not be a major factor for tumor immune evasion in multiple myeloma
Indoleamine 2,3-dioxygenase (IDO) may not be a major factor for tumor immune evasion in multiple myeloma
?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.
multiple-myeloma, myeloma, vaccine, time, 50, tumor, immune evasion
0390-6078
PO-241
Zojer, N.
5dec9dcd-c973-44e7-80c5-28b6f62713f9
Schreder, M.
7e8e8881-0113-4657-a74d-f8b07b13544b
Graffi, S.
d335392b-53c4-4784-b4f1-a6a3f49bb446
Fuchs, D.
bdb5de54-9226-40ce-a13d-fcb1d9ed3618
Sahota, S.
66c1457f-cba2-4c49-9c8c-fcee0748b6b8
Ludwig, H.
ff5c3f7b-d92f-411f-9e6a-53aa8fca4335
Zojer, N.
5dec9dcd-c973-44e7-80c5-28b6f62713f9
Schreder, M.
7e8e8881-0113-4657-a74d-f8b07b13544b
Graffi, S.
d335392b-53c4-4784-b4f1-a6a3f49bb446
Fuchs, D.
bdb5de54-9226-40ce-a13d-fcb1d9ed3618
Sahota, S.
66c1457f-cba2-4c49-9c8c-fcee0748b6b8
Ludwig, H.
ff5c3f7b-d92f-411f-9e6a-53aa8fca4335

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.

Record type: Article

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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More information

Published date: June 2007
Additional Information: Published in the Abstract Book of XIth International Myeloma Workshop and the IVth International Workshop on Waldenström’s Macroglobulinemia, 25-30 June 2007 – Kos Island, Greece
Keywords: multiple-myeloma, myeloma, vaccine, time, 50, tumor, immune evasion

Identifiers

Local EPrints ID: 62978
URI: http://eprints.soton.ac.uk/id/eprint/62978
ISSN: 0390-6078
PURE UUID: d945d8a2-f44c-4926-a927-85dde4e18b39

Catalogue record

Date deposited: 11 Sep 2008
Last modified: 11 Dec 2021 18:09

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Contributors

Author: N. Zojer
Author: M. Schreder
Author: S. Graffi
Author: D. Fuchs
Author: S. Sahota
Author: H. Ludwig

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