Health TrialsbyHealthPanel

Decoding Epigenetic Mechanisms Driving Immune Evasion in Liver Cancer With Omics Approaches

ConditionHepatocarcinoma
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorNiguarda Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

None

Trial population

Patients with HCC and eligible for biopsy or surgical resection

Trial design

Design model

Other

Time perspective

Retrospective

Treatments tested in this trial

  • Collection of tumor tissue (Fresh or/and archival FFPE), blood samples

    Genetic

    NGS, immunofluorescence analyses, transcriptional and immunophenotypic analyzes, scRNAseq, ChIP-seq/ATAC-seq, DNA methylation, single-cell transcriptomic and TCR sequencing

Treatment groups

270 Participants
are divided into 1 treatment group
Group A: HCC patients1 intervention

Trial outcomes

Primary outcomes

1

Characterize the molecular mechanisms underlying T cell dysfunction

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.

Time frame
5 years

Secondary outcomes

1

Analyze the epigenetic transcriptional regulatory mechanisms

To analyze the epigenetic and transcriptional regulatory mechanisms mediated by the newly identified transcripts from the primary objective, including TEcontaining transcripts, in the cellular components of the HCC tumor microenvironment. Mapping of the genomic occupancy, epigenetic landscape, and three-dimensional chromatin conformation associated with the newly identified regulatory transcripts, including those containing TEs, in TME cells, with particular attention to TILs.

Time frame
5 years
2

Retrospective analysis on FFPE samples

Evaluation of the expression dynamics of regulatory transcripts, including those containing TEs, as potential predictive biomarkers of response to immunotherapy, through retrospective analysis on FFPE tissue samples.

Time frame
5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Niguarda Hospital

Lead sponsor

San Raffaele University Hospital, Italy

Collaborator

Fondazione Istituto Nazionale Genetica Molecolare - INGM

Collaborator

University of Milan

Collaborator

Source ClinicalTrials.gov
Apply now