title: Demethylation of the TSDR is a marker of squamous cell carcinoma in transplant recipients.
abstract: 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.
authors.affiliation: Transplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: S N
authors.initials: SN
authors.lastname: Sherston
authors.forename: K
authors.initials: K
authors.lastname: Vogt
authors.forename: S
authors.initials: S
authors.lastname: Schlickeiser
authors.forename: B
authors.initials: B
authors.lastname: Sawitzki
authors.forename: P N
authors.initials: PN
authors.lastname: Harden
authors.forename: K J
authors.initials: KJ
authors.lastname: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D014180:Transplantation / Q000009:adverse effects*
chemical_list: D014408:Biomarkers, Tumor; D007166:Immunosuppressive Agents
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