Mechanisms of Lymphomagenesis of Skin Resident Gamma Delta T cells

项目总结 原发性皮肤伽马三角洲T细胞淋巴瘤(PCGDTL)是一种高度侵袭性的、不可治愈的 皮肤归巢γδT细胞的非霍奇金淋巴瘤。中位生存期为31个月。五年生存率为19.9%。 在对疾病病理生理学缺乏基本了解的情况下，在过去的几年中几乎没有取得什么进展 几十年。一个关键的未得到满足的需求是通过阐明基础疾病来发现新的治疗靶点 机械装置。淋巴瘤的表型由体细胞突变和起源细胞共同决定。 为了阐明PCGDTL的基因组、转录和细胞起源，我们组装了一个大型的、多个- 代表不同临床表型的机构样本队列。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 这些研究代表着一个偶然的机会来阐明驻留在皮肤上的伽马三角洲T细胞的生物学， 人类皮肤中一种知之甚少但可能很重要的淋巴细胞。

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.