Journal Article

Conversion to sirolimus in kidney transplant recipients with squamous cell cancer and changes in immune phenotype

Robert P. Carroll, Joanna Hester, Kathryn J. Wood and Paul N. Harden

in Nephrology Dialysis Transplantation

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

Volume 28, issue 2, pages 462-465
Published in print February 2013 | ISSN: 0931-0509
Published online December 2012 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfs474

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Background

Conversion to sirolimus from calcineurin inhibitor- (CNI), azathioprine- (AZA) and mycophenolate-based regimens reduces the risk of development of squamous cell carcinoma of the skin (SCC) in kidney transplant recipients (KTRs). Sirolimus conversion may also be protective by permitting beneficial changes in immune phenotype. It is not known how sirolimus will affect immune phenotype in KTRs with SCC.

Methods

Thirty-two KTRs with SCC were enrolled into this single-blinded randomized study and 13 KTRs randomized to sirolimus (4–10 ng/mL) and prednisolone 5 mg/day.

Results

Six-month post conversion to sirolimus FOXP3+ CD127lowCD25highCD69, the number of T cells (putative Treg) increased significantly (P = 0.008). Natural killer (NK) and CD56bright NK cells also increased significantly (P = 0.039 and 0.02). T-cell number only significantly increased in those KTRs where CNI was ceased as part of the conversion to mammalian target of rapamycin inhibitors (mTORi's) (P = 0.031) implying CNI cessation rather than mTORi initiation induced an increase in T-cell number. Increases in the NK cell number was only significant in those KTRs where AZA was ceased (P = 0.040), implying AZA cessation rather than mTORi initiation caused the NK cell number to increase. At 6 months, sirolimus conversion reduces new SCC/year, rate ratio 0.49 (95%CI: 0.15–1.63), P = 0.276. On therapy analysis and intention-to-treat analysis over 24 months, the rate ratios were 0.84 and 0.87, respectively, and did not reach significance.

Conclusions

Conversion to mTORi from CNI may reveal a pre-existing high Treg phenotype by unmasking CNI inhibition of FOXP3 expression. Cessation of AZA leads to increased NK cell number. High FOXP3+ T-cell number on conversion to mTORi may predict those KTRs who continue to accrue SCC.

Keywords: immune phenotype; mTOR inhibitors; skin cancer; Treg

Journal Article.  2173 words.  Illustrated.

Subjects: Nephrology

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