Decoding Epigenetic Mechanisms Driving Immune Evasion in Liver Cancer With Omics Approaches
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 270
- 试验地点
- 1
- 主要终点
- Characterize the molecular mechanisms underlying T cell dysfunction
研究概览
简要总结
This is a national, observational, retrospective, cross-sectional, non-profit study focused on patients with HCC. The study aims to characterize the expression and function of novel noncoding regulatory transcripts, including those containing TEsin the microenvironment of liver tumors, with emphasis on their role in T cell dysfunction.
详细描述
We will use TILs, along with other immune, hepatocyte, and stromal cell populations isolated from hepatocellular carcinoma (HCC) tissue, matched adjacent non-tumoral liver, and peripheral blood samples. Single-cell RNA sequencing and spatial transcriptomics will be employed to define the cellular distribution and molecular profiles of TE-containing transcripts, other noncoding RNAs, and associated gene expression programs within the HCC microenvironment. Functional experiments-including CRISPR-Cas13 or ASO-mediated silencing-will be performed to elucidate the role of the novel regulatory transcripts, including TE-transcripts, in modulating cellular identity within the liver TME. In parallel, epigenetic analyses such as ChIPseq, ATAC-seq, DNA methylation profiling, RADICL-seq, and Hi-C will be conducted to map the regulatory networks and chromatin architecture associated with these transcripts
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological/radiological (LR-4 o 5)diagnosis of hepatocellular carcinoma (HCC).
- •Solid tumor fresh tissue availability from HCC biospy or surgical resectionas per standard clinical practice, and/orHCC FFPE archival samples availability.
- •Capability of understanding and signing an inform consent form.
- •Known hepatits B and C status, including HBeAg (positive or negative), viral load (HBVDNA e HCV-RNA), HCV genotype, whether sustained virological response (SVR)was obtainedand potential antiviral treatments received (including direct antiretroviral therapy(DAA)and interferon). These parameters will be exploited to stratify patients and analyze the impact of the virological status on microenvironmental immunological features, with particular regards to immunesuppression mechanisms.
排除标准
- 未提供
研究组 & 干预措施
HCC patients
120 patients will be prospectively recruitedand from whom fresh tumor samples and blood samples will be collected. 150 HCC patients treated by surgery FFPE samples will be retrospectively collected
干预措施: Collection of tumor tissue (Fresh or/and archival FFPE), blood samples (Genetic)
结局指标
主要结局
Characterize the molecular mechanisms underlying T cell dysfunction
时间窗: 5 years
To characterize the molecular mechanisms underlying T cell dysfunction and immune evasion in the tumor microenvironment of hepatocellular carcinoma, through the identification and functional definition of novel non-coding regulatory transcripts - including those containing transposable elements - expressed at single-cell resolution. Identification of TE-containing transcripts expressed in tumor-infiltrating lymphocytes (TILs) and other cellular populations within the HCC tumor microenvironment, using single-cell transcriptomics (scRNA-seq) and spatial transcriptomics technologies.
次要结局
- Analyze the epigenetic transcriptional regulatory mechanisms(5 years)
- Retrospective analysis on FFPE samples(5 years)