Translational Oncology 45 (2024) 101961 - A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

Oct 3, 2026

Tumor microenvironment in hepatocellular carcinoma forms an immune-suppressive barrier that limits emerging immune therapies. This study identifies immune evasion mechanisms driven by HCC cells and evaluates epigenetic modulation of checkpoint signaling at the tumor-immune synapse. PD-1/PD-L1 and TIGIT/CD155 axes were screened using liver tissues, PBMCs, and sera from HCV, HCC, and healthy individuals, alongside profiling of dysregulated lncRNAs and microRNAs that regulate these checkpoints.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

Background on hepatocellular carcinoma and immune suppression

Translational Oncology 45 (2024) 101961 Contents lists available at ScienceDirect Translational Oncology journal [homepage:](homepage: www.elsevier.com/locate/tranon)[ www.elsevier.com/locate/tranon](homepage: www.elsevier.com/locate/tranon) | A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma
Reem A. Assala, Noha M. Elemamb, c, Radwa Y. Mekky d, Abdelrahman A. Attiae, Aya Hesham Solimanf, Asmaa Ibrahim Gomaag, Eleni K. Efthimiadouh, Maria Braoudakii, Sherif Ashraf Fahmyj, Rana A. Youness f, k, *
a Department of Pharmacology and Toxicology, Heliopolis University for Sustainable Development, Cairo–Ismailia Desert Road, 11785, Cairo, Egypt b Clinical Sciences Department, College of Medicine, University of Sharjah, 27272, Sharjah, United Arab Emirates
c Research Institute for Medical and Health Sciences, University of Sharjah, 27272, Sharjah, United Arab Emirates
d Department of Pharmacology and Toxicology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA University), Cairo, Egypt e General Surgery Department, Ain Shams University, Demerdash Hospital, Cairo, Egypt
f Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt g Department of Hepatology, National Liver Institute, Menoufiya University, Shebin El-Kom, Egypt
h Inorganic Chemistry Laboratory, Chemistry Department, National and Kapodistrian University of Athens, Athens, Greece
i Department of Clinical, Pharmaceutical, and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK j Chemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, 11835, Cairo, Egypt
k Molecular Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), New Administrative Capital, 11835, Cairo, Egypt | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords:
Immune checkpoint inhibitors (ICI) Programmed death-ligand 1 (PD-L1) T cell immunoreceptor with Ig and ITIM domains (TIGIT)
MALAT-1
H19
CCAT-1
HCC | | Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD- 1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944–5p, miR-105–5p, miR-486–5p, miR-506–5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs—CCAT-1, MALAT-1, or H19—markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of cocultured primary immune cells. On the immune side, ectopic expression o

FAQs

What immune checkpoint targets are studied in hepatocellular carcinoma?

The study focuses on PD-1/PD-L1 and TIGIT/CD155 axes at the tumor-immune synapse.

How were immune checkpoint-related biomarkers analyzed?

Liver tissues, PBMCs, and sera were collected from HCV, HCC, and healthy individuals, and PD-L1/PD-1 and CD155/TIGIT were screened.

Which epigenetic molecules were found to influence checkpoint expression and immune activity?

CCAT-1, H19, and MALAT-1 were upregulated, while multiple microRNAs were downregulated; knockdown or ectopic expression altered PD-L1/PD-1 and CD155/TIGIT co-expression and modulated PBMC cytotoxicity.

Oct 3, 2026

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