Journal Article

Renal transplant recipients have elevated frequencies of circulating myeloid-derived suppressor cells

Barry D. Hock, Katarzyna A. Mackenzie, Nicholas B. Cross, Karen G. Taylor, Margaret J. Currie, Bridget A. Robinson, Jeremy W. Simcock and Judith L. McKenzie

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 1, pages 402-410
Published in print January 2012 | ISSN: 0931-0509
Published online May 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr264
Renal transplant recipients have elevated frequencies of circulating myeloid-derived suppressor cells

Show Summary Details

Preview

Background.

Cancer, particularly cutaneous squamous cell carcinoma (SCC), is a major cause of mortality in renal transplant recipients (RTRs). Myeloid-derived suppressor cells (MDSC) play a central role in suppressing cancer immunosurveillance but their potential mobilisation in RTRs and levels relative to those of other immunoregulatory dendritic cell (DC) populations have not been analysed.

Methods.

The circulating frequencies of MDSC and DC were analysed by multicolour flow cytometry in immunocompetent patients without (n = 13) or with (ICI-SCCPos, n = 14) current SCC, normal donors (NDs, n = 34), chronic kidney disease patients (CKD patients, n = 22) and RTRs (n = 31).

Results.

Compared to NDs, RTRs had significantly elevated levels of both CD14Neg and CD14Pos MDSC subsets (P < 0.001), while CKD patients and ICI-SCCPos had significantly elevated levels of only the CD14Neg-MDSC subset. DC frequencies were significantly decreased in RTRs and CKD patients but were at normal levels in ICI-SCCPos. The MDSC/DC ratio was significantly elevated (P < 0.05) in RTRs (median = 5.7), CKD patients (median = 3.2) and ICI-SCCPos (median = 3.5) relative to NDs (median = 0.7). The use of immunosuppressive drugs in CKD patients and past/current occurrence of SCC in RTRs was associated with significantly increased CD14Neg-MDSC frequencies. MDSC enriched from RTRs, when co-cultured with activated NDs T cells significantly suppressed extracellular IL-10 levels and can, when activated with formyl-methionyl-leucyl-phenylalanine, inhibit T-cell proliferation.

Conclusions.

RTRs, CKD patients and ICI-SCCPos have increased MDSC frequencies and MDSC/DC ratios. These changes may impact on cancer immunosurveillance. Therefore, MDSC represent both a potential therapeutic target and prognostic marker in these patients, with respect to the development of SCC and other malignancies.

Keywords: dendritic cell; myeloid-derived suppressor cells; renal; transplant; squamous; cell; carcinoma

Journal Article.  4593 words.  Illustrated.

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.