Investigation of the role of B cells and the tolerance signature in cutaneous squamous cell carcinoma in renal transplant recipients. (360G-Wellcome-098744_Z_12_Z)

Transplantation is the only long term solution for organ failure, but requires lifelong immunosuppression. Kidney transplant recipients (KTR) are at significantly higher risk of malignancy, in particular cutaneous squamous cell carcinoma (SCC). A previous study by this group demonstrated that KTRs who develop multiple SCCs have a distinct immune phenotype, characterised by increased levels of regulatory T cells (Treg) in peripheral blood and around the tumour. Recently a 'signature' assoc iated with the development of graft tolerance has been described in KTR. This signature had a high sensitivity and specificity when tested on an independent cohort and implicated a B cell subset with regulatory capabilities (Breg) in playing a major role in tolerance development. However, Breg are required for carcinogenesis in a number of animal models, including SCC. These cells stimulate the proliferation of Treg in vitro. We hypothesise that the development SCC in KTR may be associated with the presence of the tolerance signature. We will recruit KTR who do and do not develop SCC. We will test for the presence of the signature in peripheral blood and analyse Breg phenotype and function in vitro. We will study excised SCC to assess Breg levels around the tumour.