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Mechanisms of Lymphomagenesis of Skin Resident Gamma Delta T cells

皮肤驻留 Gamma Delta T 细胞的淋巴瘤发生机制

基本信息

批准号：
10540385
负责人：
Jaehyuk Choi
金额：
$ 45.33万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-13 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10540385
关键词：
Anatomy Automobile Driving BCL6 gene Biological Biological Markers Biology CD4 Positive T Lymphocytes Cells Cellular immunotherapy Clinical Clinical Management Collection Cutaneous Cutaneous Lymphoma Cutaneous T-cell lymphoma D Cells DNA sequencing Data Dermal Dermis Development Disease Disease Management Enzymes Epidermis Fatty acid glycerol esters Functional disorder Future Gene Mutation Genes Genetic Genetic Markers Genetic Transcription Genomics Goals Hemophagocytic Lymphohistiocytoses Homing Human Immunologics Immunology Immunophenotyping Inflammatory Institution Interferon Type II Knowledge Life Lymphocyte Lymphoma Lymphomagenesis MAP Kinase Gene Malignant Neoplasms Molecular Molecular Analysis Morbidity - disease rate Mutation Non-Hodgkin&apos s Lymphoma Organ Patients Pattern Phenotype Physiological Prognosis RHOA gene Research Sampling Skin Skin Cancer Somatic Cell Somatic Mutation Southern Blotting Stimulus Syndrome T-Cell Lymphoma Testing Time Tissues Tumor Burden Visceral antibody mimetics clinical heterogeneity clinical phenotype clinically actionable cohort cytokine disease phenotype disease prognosis effective therapy familial hemophagocytic lymphohistiocytosis high dimensionality mortality mutant new therapeutic target novel receptor therapeutic target transcription factor transcriptome sequencing γδ T cells

项目摘要

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.

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。