Mechanisms of Lymphomagenesis of Skin Resident Gamma Delta T cells

项目摘要 原发性皮肤γ δ T细胞淋巴瘤（PCGDTLs）是一组高度侵袭性、不可治愈的 皮肤归巢γδ T细胞非霍奇金淋巴瘤。中位生存期为31个月。5年生存率为19.9%。 由于没有对疾病病理生理学的基本理解， 几十年一个关键的未满足的需求是通过阐明基础疾病来发现新的治疗靶点 机制等淋巴瘤表型由体细胞突变和细胞起源的组合决定。 为了阐明PCGDTLs的基因组，转录和细胞起源，我们组装了一个大的，多- 代表不同临床表型的样本的机构队列。通过分析高维基因组 和免疫学数据，我们假设我们可以确定这种疾病的分子基础。重要的是， 这些研究代表了阐明皮肤驻留γ δ T细胞的生物学的偶然机会， 一种人们知之甚少但可能很重要的人体皮肤淋巴细胞。

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.