The Role of Epstein-Barr Virus in Mycosis Fungoides (360G-Wellcome-207098_Z_17_Z)

Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma, a group of T cell cancers that generally affect the skin. Lesions/plaques arise in MF patients due to clonal expansion of epidermis-homing memory CD4+ T cell populations and the inflammation that accompanies this expansion. While the underlying cause of MF remains unknown, there is a strong association in a subset of MF with the common herpesvirus Epstein-Barr virus (EBV). The aim of this project is to investigate the impact of EBV on the phenotype and function of transformed CD4+ T cells isolated from skin lesions of MF patients. EBV positivity will be confirmed by qPCR of MF lesions. In cases which are EBV-positive, immune cells will be recovered from skin biopsies by mechanical and/or enzymatic digestion. Fluorescence in situ hybridisation (FISH) will be used to detect EBV-encoded small RNAs (EBERs) inside CD4+ T cells. This, in combination with staining for markers that identify CD4+ T cell subsets (naïve vs memory, cytotoxic, Treg, amongst others) will reveal the phenotype of the transformed cells. Finally, we will test the susceptibility of the isolated tumour cells to novel chemotherapeutic drugs and small molecule inhibitors.