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：
10375244
负责人：
Jaehyuk Choi
金额：
$ 51.36万
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/10375244
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 DNA sequencing Data Dermal Dermis Development Disease Disease Management Enzymes Epidermis Fatty acid glycerol esters Functional disorder Future Gene Mutation Genes Genetic Genetic Drift Genetic Markers Genetic Transcription Genomics Goals Homing Human Immunologics Immunology Immunophenotyping Inflammatory 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 base 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.

项目概要原发性皮肤 γ δ T 细胞淋巴瘤 (PCGDTL) 是一组高度侵袭性、无法治愈的疾病皮肤归巢 γδ T 细胞的非霍奇金淋巴瘤的中位生存期为 31 个月，五年生存率为 19.9%。由于缺乏对疾病病理生理学的基本了解，过去几年几乎没有取得任何进展。几十年来，一个未满足的关键需求是通过阐明基本疾病来发现新的治疗靶点。淋巴瘤表型是由体细胞突变和细胞起源共同决定的。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，我们努力确定这种疾病的分子基础。这些研究为阐明皮肤驻留性 γ δ T 细胞的生物学提供了一个偶然的机会，人类皮肤中的一种人们知之甚少但可能很重要的淋巴细胞。