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Malignancy is an important cause of death in transplant recipients. Cutaneous squamous cell carcinoma (cSCC) causes significant morbidity and mortality as 30% of transplant recipients will develop cSCC within 10 years of transplantation. Previously we have shown that high numbers of regulatory T cells (Tregs) are associated with the development of cSCC in kidney transplant recipients (KTRs). Demethylation analysis of the Treg-specific demethylated region (TSDR) provides a more accurate association with cSCC risk after transplantation. Age, gender and duration of immunosuppression matched KTRs with (n=32) and without (n=27) cSCC, were re-analyzed for putative clinical and immunological markers of cancer risk. The proportion of FOXP3+ CD4+ cells was higher in the population with a previous SCC. Major T cell subsets remained stable over time; although B cell, CD8 and CD4 subpopulations demonstrated age-related changes. TSDR methylation analysis allowed clarification of Treg numbers, enhancing the association of high Treg levels in KTRs with cSCC compared to the cSCC-free cohort. These data validate and expand on previous findings in long-term KTRs, and show that immune markers remain stable over time. TSDR demethylation analysis provides a more accurate biomarker of cancer posttransplantation.

Original publication

DOI

10.1111/ajt.12899

Type

Journal article

Journal

Am J Transplant

Publication Date

11/2014

Volume

14

Pages

2617 - 2622

Keywords

Basic (laboratory) research/science, biomarker, cancer/malignancy/neoplasia: skin, flow cytometry, immune regulation, immunobiology, kidney transplantation/nephrology, monitoring: immune, nonmelanoma, organ transplantation in general, translational research/science, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Squamous Cell, DNA Methylation, Female, Humans, Immunosuppressive Agents, Male, Middle Aged, Transplantation