Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy

Liver cancer, particularly hepatocellular carcinoma (HCC), is one of the most common and aggressive malignancies worldwide. Immunotherapy has shown promising results in treating HCC, but its efficacy is often limited by complex mechanisms of immune evasion. Post-translational modifications (PTMs) of...

Full description

Saved in:
Bibliographic Details
Main Authors: Yuexian Piao, Naicui Zhai, Xiaoling Zhang, Wenjie Zhao, Min Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1554372/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850087163920646144
author Yuexian Piao
Naicui Zhai
Xiaoling Zhang
Xiaoling Zhang
Wenjie Zhao
Wenjie Zhao
Min Li
author_facet Yuexian Piao
Naicui Zhai
Xiaoling Zhang
Xiaoling Zhang
Wenjie Zhao
Wenjie Zhao
Min Li
author_sort Yuexian Piao
collection DOAJ
description Liver cancer, particularly hepatocellular carcinoma (HCC), is one of the most common and aggressive malignancies worldwide. Immunotherapy has shown promising results in treating HCC, but its efficacy is often limited by complex mechanisms of immune evasion. Post-translational modifications (PTMs) of proteins play a critical role in regulating the immune responses within the tumor microenvironment (TME). These modifications influence protein function, stability, and interactions, which either promote or inhibit immune cell activity in cancer. In this mini-review, we explore the diverse PTMs that impact immune evasion in liver cancer, including glycosylation, phosphorylation, acetylation, and ubiquitination. We focus on how these PTMs regulate key immune checkpoint molecules such as PD-L1, CTLA-4, and the TCR complex. Furthermore, we discuss the potential of targeting PTMs in combination with existing immunotherapies to enhance the effectiveness of treatment in HCC. Understanding the role of PTMs in immune regulation may lead to the development of novel therapeutic strategies to overcome resistance to immunotherapy in liver cancer.
format Article
id doaj-art-ba6e4bacdd324d14927b4c7f39541d62
institution DOAJ
issn 1664-3224
language English
publishDate 2025-02-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-ba6e4bacdd324d14927b4c7f39541d622025-08-20T02:43:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15543721554372Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapyYuexian Piao0Naicui Zhai1Xiaoling Zhang2Xiaoling Zhang3Wenjie Zhao4Wenjie Zhao5Min Li6Department of Interventional Therapy, First Hospital of Jilin University, Changchun, ChinaCore Facility of First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, ChinaDepartment of Interventional Therapy, First Hospital of Jilin University, Changchun, ChinaLiver cancer, particularly hepatocellular carcinoma (HCC), is one of the most common and aggressive malignancies worldwide. Immunotherapy has shown promising results in treating HCC, but its efficacy is often limited by complex mechanisms of immune evasion. Post-translational modifications (PTMs) of proteins play a critical role in regulating the immune responses within the tumor microenvironment (TME). These modifications influence protein function, stability, and interactions, which either promote or inhibit immune cell activity in cancer. In this mini-review, we explore the diverse PTMs that impact immune evasion in liver cancer, including glycosylation, phosphorylation, acetylation, and ubiquitination. We focus on how these PTMs regulate key immune checkpoint molecules such as PD-L1, CTLA-4, and the TCR complex. Furthermore, we discuss the potential of targeting PTMs in combination with existing immunotherapies to enhance the effectiveness of treatment in HCC. Understanding the role of PTMs in immune regulation may lead to the development of novel therapeutic strategies to overcome resistance to immunotherapy in liver cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1554372/fullpost-translation modificationimmunotherapyhepatocellular carcinomalactylationglycosylation
spellingShingle Yuexian Piao
Naicui Zhai
Xiaoling Zhang
Xiaoling Zhang
Wenjie Zhao
Wenjie Zhao
Min Li
Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy
Frontiers in Immunology
post-translation modification
immunotherapy
hepatocellular carcinoma
lactylation
glycosylation
title Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy
title_full Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy
title_fullStr Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy
title_full_unstemmed Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy
title_short Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy
title_sort post translational modifications in hepatocellular carcinoma unlocking new frontiers in immunotherapy
topic post-translation modification
immunotherapy
hepatocellular carcinoma
lactylation
glycosylation
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1554372/full
work_keys_str_mv AT yuexianpiao posttranslationalmodificationsinhepatocellularcarcinomaunlockingnewfrontiersinimmunotherapy
AT naicuizhai posttranslationalmodificationsinhepatocellularcarcinomaunlockingnewfrontiersinimmunotherapy
AT xiaolingzhang posttranslationalmodificationsinhepatocellularcarcinomaunlockingnewfrontiersinimmunotherapy
AT xiaolingzhang posttranslationalmodificationsinhepatocellularcarcinomaunlockingnewfrontiersinimmunotherapy
AT wenjiezhao posttranslationalmodificationsinhepatocellularcarcinomaunlockingnewfrontiersinimmunotherapy
AT wenjiezhao posttranslationalmodificationsinhepatocellularcarcinomaunlockingnewfrontiersinimmunotherapy
AT minli posttranslationalmodificationsinhepatocellularcarcinomaunlockingnewfrontiersinimmunotherapy