Characterizing the immune and metabolic profiles of cutaneous T-cell lymphoma in formalin-fixed paraffin-embedded skin tissue samples
表征福尔马林固定石蜡包埋皮肤组织样本中皮肤 T 细胞淋巴瘤的免疫和代谢特征
基本信息
- 批准号:10058252
- 负责人:
- 金额:$ 3.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-01 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
PROJECT SUMMARY/ABSTRACT
Cutaneous T-cell lymphoma (CTCL) is a rare, but potentially devastating malignancy of the skin.
Early detection of CTCL is associated with positive clinical outcomes, but diagnosis is often complicated
by the heterogeneous clinical and histological presentation. Additionally, systemic therapies remain sub-
optimal for CTCL, highlighting the need for new treatment strategies. To date, most studies have been
performed on blood from CTCL patients, which has revealed a complex interplay between host immunity,
malignant T-cells and the tumor microenvironment. However, the molecular mechanisms that govern
disease pathogenesis, especially in the skin, remain largely undefined.
The goal of the proposed research is to use new technologies that allow for multi-parametric, high-
resolution analyses in formalin-fixed paraffin-embedded (FFPE) skin tissue samples to define the immune
and metabolic profiles of CTCL at different stages of disease. The first technology is Multiplexed Ion Beam
Imaging (MIBI), which uses secondary ion mass spectrometry to visualize up to 100 metal conjugated
antibodies simultaneously at nanometer resolution in FFPE tissue sections. Specifically, Aim I will use
MIBI to define the heterogeneity and plasticity of cells that exist at the CTCL tumor-host interface, to
improve the precision with which CTCL is diagnosed and treated. The second technology is matrix-assisted
laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which can detect thousands of
metabolites in FFPE tissue sections. Specifically, Aim II will use MALDI-MSI to determine the reflective
metabolic activity of the CTCL microenvironment, thereby adding functional insight to disease
pathogenesis and revealing potential metabolically active therapeutic targets.
Overall, these studies will characterize the molecular heterogeneity and functional complexity of
CTCL, which will shed light on how this disease evades immune destruction and reprograms energy-
metabolism. As such, this work promises to improve the detection, treatment and clinical outcomes for
CTCL.
项目摘要/摘要
皮肤T细胞淋巴瘤(CTCL)是皮肤的罕见但可能具有毁灭性的恶性肿瘤。
CTCL的早期检测与阳性临床结果有关,但诊断通常很复杂
由异质临床和组织学表现。此外,全身疗法仍然是
CTCL的最佳选择,强调了对新治疗策略的需求。迄今为止,大多数研究已经
在CTCL患者的血液上进行的,这表明宿主免疫之间存在复杂的相互作用,
恶性T细胞和肿瘤微环境。但是,控制的分子机制
疾病的发病机理,尤其是在皮肤中,在很大程度上仍然不确定。
拟议的研究的目的是使用允许多参数,高级技术的新技术
在福尔马林固定石蜡包裹(FFPE)皮肤组织样品中进行分辨率分析以定义免疫
在疾病的不同阶段,CTCL的代谢谱。第一个技术是多路复用的离子束
成像(MIBI),它使用二级离子质谱法可视化多达100个金属共轭
FFPE组织切片中纳米分辨率同时抗体。具体来说,目标我将使用
MIBI定义CTCL肿瘤宿主界面上存在的细胞的异质性和可塑性,
提高CTCL诊断和处理的精度。第二种技术是矩阵辅助的
激光解吸/电离质谱成像(MALDI-MSI),可以检测数千个
FFPE组织切片中的代谢产物。具体而言,AIM II将使用MALDI-MSI来确定反思性
CTCL微环境的代谢活性,从而为疾病增加了功能洞察力
发病机理并揭示潜在的代谢活性治疗靶标。
总体而言,这些研究将表征分子异质性和功能复杂性
CTCL将阐明这种疾病如何逃避免疫破坏并重新编程。
代谢。因此,这项工作有望改善检测,治疗和临床结果
CTCL。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

暂无数据
数据更新时间:2024-06-01
相似国自然基金
募集HBV抗体用于肿瘤免疫治疗的分子设计及作用机制
- 批准号:22377041
- 批准年份:2023
- 资助金额:50 万元
- 项目类别:面上项目
双特异性抗体囊泡对胞内细菌感染的免疫综合机制研究
- 批准号:82304366
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
四种停用喹诺酮类药物高分辨力单克隆抗体的精准制备及其识别机制研究
- 批准号:32373059
- 批准年份:2023
- 资助金额:50 万元
- 项目类别:面上项目
DHEA协同别构纳米抗体通过ADGRG2调控男性生殖功能障碍的作用及机制
- 批准号:82371629
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
靶向DLL3和γδ T细胞的双特异抗体对小细胞肺癌的免疫治疗活性研究
- 批准号:32300783
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Development of contrast agents to facilitate image-guided surgery
开发造影剂以促进图像引导手术
- 批准号:1081018410810184
- 财政年份:2023
- 资助金额:$ 3.86万$ 3.86万
- 项目类别:
A First-in-class Topical Immunoregulatory Therapeutic for Psoriasis
一流的牛皮癣局部免疫调节疗法
- 批准号:1082033110820331
- 财政年份:2023
- 资助金额:$ 3.86万$ 3.86万
- 项目类别:
Extratumoral biological determinants that decrease survival in older adults with glioblastoma
降低老年胶质母细胞瘤患者生存率的肿瘤外生物决定因素
- 批准号:1074138010741380
- 财政年份:2023
- 资助金额:$ 3.86万$ 3.86万
- 项目类别:
Emerging Cellular Therapies at the Forefront of Cancer Immunotherapy
处于癌症免疫治疗前沿的新兴细胞疗法
- 批准号:1054049610540496
- 财政年份:2023
- 资助金额:$ 3.86万$ 3.86万
- 项目类别:
Molecular and Cellular Pathogenesis of Pulmonary Langerhans Cell Histiocytosis
肺朗格汉斯细胞组织细胞增多症的分子和细胞发病机制
- 批准号:1065820810658208
- 财政年份:2023
- 资助金额:$ 3.86万$ 3.86万
- 项目类别: