Mechanisms of Lymphomagenesis of Skin Resident Gamma Delta T cells

PROJECT SUMMARY Primary cutaneous gamma delta T cell lymphomas (PCGDTLs) are a collection of highly aggressive, incurable non-Hodgkin lymphoma of the skin-homing γδ T cell. Median survival is 31 months. Five-year survival is 19.9%. Without a fundamental understanding of disease pathophysiology, there has been little progress in the last few decades. A critical unmet need is to uncover novel therapeutic targets via elucidation of basic disease mechanisms. Lymphoma phenotypes are determined by a combination of somatic mutations and cell of origin. To elucidate the genomic, transcriptional, and cellular origins of PCGDTLs, we have assembled a large, multi- institutional cohort of samples representing diverse clinical phenotypes. By analyzing high-dimensional genomic and immunological data, we hypothesize that we can identify the molecular basis of this disease. Importantly, these studies represent a serendipitous opportunity to elucidate the biology of skin-resident gamma delta T cells, a poorly understood but likely important lymphocyte in human skin.