biostudies-literatureUnknown197(3)Peters FSCutaneous squamous cell carcinoma (cSCC) is a serious complication after organ transplantation and patients benefit from an early risk assessment. We hypothesized that functional differences in circulating T cells may represent risk factors for post-transplant cSCC development. Here, we analysed genome-wide DNA methylation of circulating T cells of kidney transplant recipients before the clinical onset of cSCC, to identify differences associated with post-transplant cSCC development. This analysis identified higher DNA methylation of SERPINB9, which is an intracellular inhibitor of granzyme B, a protein that induces apoptosis in target cells. High DNA methylation of SERPINB9 in circulating T cells was confirmed in a second patient cohort during recurrent cSCC, indicating that high SERPINB9Clinical and experimental immunology341-351https://www.ebi.ac.uk/biostudies/studies/S-EPMC6693965biostudies-literatureDisrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer.PMC6693965Peters FSMooyaart ALvan de Wetering Jvan den Bosch TPPPeeters AMABetjes MGHBaan CCBoer KfalseDisrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer.Cutaneous squamous cell carcinoma (cSCC) is a serious complication after organ transplantation and patients benefit from an early risk assessment. We hypothesized that functional differences in circulating T cells may represent risk factors for post-transplant cSCC development. Here, we analysed genome-wide DNA methylation of circulating T cells of kidney transplant recipients before the clinical onset of cSCC, to identify differences associated with post-transplant cSCC development. This analysis identified higher DNA methylation of SERPINB9, which is an intracellular inhibitor of granzyme B, a protein that induces apoptosis in target cells. High DNA methylation of SERPINB9 in circulating T cells was confirmed in a second patient cohort during recurrent cSCC, indicating that high SERPINB92019-01-01T00:00:00Z2019 Sep2026-05-07T18:07:48.622Z2019-08-23T07:04:51ZS-EPMC66939653105912810.1111/cei.13309