VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8+T cells function in the HCC microenvironment DOI Creative Commons
Cheng Cheng,

Qingrui Zha,

Linmao Sun

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 23, 2025

Abstract CD8 + T cells within the tumor microenvironment (TME) are often functionally impaired, which limits their ability to mount effective anti-tumor responses. However, molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of suppression in hepatocellular carcinoma (HCC). Our findings reveal that VCP suppresses activation, expansion, and cytotoxic capacity both vitro vivo, significantly contributing immunosuppressive nature TME. Mechanistically, stabilizes expression glycerol-3-phosphate dehydrogenase 1-like (GPD1L), leading accumulation (G3P), downstream metabolite GPD1L. The accumulated G3P diffuses into TME directly interacts with SRC-family tyrosine kinase LCK, critical component T-cell receptor (TCR) signaling pathway cells. This interaction heightens phosphorylation Tyr505, inhibitory residue, ultimately reducing LCK activity impairing TCR signaling. Consequently, lose functional capacity, diminishing fight against HCC. Importantly, demonstrated targeting combination anti-PD1 therapy HCC growth restores function cells, suggesting synergistic therapeutic potential. These highlight previously unrecognized mechanism involving suppressing T-cell-mediated immunity TME, positioning promising upstream target for enhancing immunotherapy

Language: Английский

Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma DOI Creative Commons

Yau-Tuen Chan,

Cheng Zhang, Junyu Wu

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 6, 2024

Language: Английский

Citations

40
Hepatocellular carcinoma: Revising the surgical approach in light of the concept of multiparametric therapeutic hierarchy DOI
Umberto Cillo, Enrico Gringeri, F. D’Amico

et al.

Digestive and Liver Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation DOI Creative Commons

Danjun Song,

Zhou Zhang,

Jiaping Zheng

et al.

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 7, 2025

Abstract Developing accurate, clinically convenient, and non-invasive methods for early cancer detection, monitoring, prognosis assessment is essential improving patient survival rates, enhancing quality of life, reducing the socioeconomic burden associated with cancer. This goal critical in precision oncology. Genetic epigenetic alterations circulating cell-free DNA (cfDNA) have emerged as transformative tools advancing outcomes. Among these, 5-hydroxymethylcytosine (5hmC) modifications cfDNA stand out promising markers, offering insights into initiation, progression, metastasis, across various types, such lung cancer, colorectal hepatocellular carcinoma. review comprehensively explores biology sequencing methodologies 5hmC, emphasizing their potential screening, diagnosis, treatment prognostic assessment. It highlights recent advancements cfDNA-derived 5hmC signatures’ applications, addressing strengths limitations context clinical translation. Furthermore, this outlines key challenges future directions integrating routine practice, facilitating personalized management.

Language: Английский

Citations

2
Dynamic prognostication and treatment planning for hepatocellular carcinoma: A machine learning-enhanced survival study using multi-centric data DOI
Lujun Shen,

Yiquan Jiang,

Linbin Lu

et al.

The Innovation Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100125 - 100125

Published: Jan. 1, 2025

<p>A reliable system for dynamic prognostication and management of hepatocellular carcinoma (HCC) is urgently needed but currently unavailable. In our previous work, we developed a machine learning algorithm termed "Survival Path" (raw-SP) to enhance with longitudinal survival data. However, the model was limited intermediate stage HCC patients, it faced risk overfitting due path proliferation. this study, novel framework incorporating nodal fusion techniques mitigate overfitting, expanded model's applicability all stages patients. A post-fusion map (fusion-SP) containing 14 different paths built, which demonstrated superior or non-inferior accuracy in prognosis prediction patients compared raw-SP, as well traditional staging systems within first 15 months since initial diagnosis large-scale derivation, internal external validation cohorts. Subgroup analysis showed fusion-SP performance other models among BCLC C disease tumor burden above up-to-seven criteria. Under fusion-SP, distinct optimal combination treatment strategies advanced-stage at key nodes were uncovered, where frameworks fall short. The could serve robust tool facilitating planning HCC. Moreover, streamlined methodology holds potential be applied across various types cancers.</p>

Language: Английский

Citations

2
The current status and future of targeted-immune combination for hepatocellular carcinoma DOI Creative Commons

Liyuan Hao,

Shenghao Li,

Fanghang Ye

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 5, 2024

Hepatocellular carcinoma (HCC) is one of the most common cancers and third leading cause death worldwide. surgery, transarterial chemoembolization (TACE), systemic therapy, local ablation radiotherapy, targeted drug therapy with agents such as sorafenib. However, tumor microenvironment liver cancer has a strong immunosuppressive effect. Therefore, new treatments for are still necessary. Immune checkpoint molecules, programmed death-1 (PD-1), death-ligand 1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), along high levels cytokines, induce cell inhibition key mechanisms immune escape in HCC. Recently, immunotherapy based on inhibitors (ICIs) monotherapy or combination tyrosine kinase inhibitors, anti-angiogenesis drugs, chemotherapy agents, topical therapies offered great promise treatment cancer. In this review, we discuss latest advances ICIs combined drugs (targeted-immune combination) other targeted-immune regimens patients advanced HCC (aHCC) unresectable (uHCC), provide an outlook future prospects. The literature reviewed spans last five years includes studies identified using keywords "hepatocellular carcinoma," "immune inhibitors," "targeted therapy," "combination "immunotherapy".

Language: Английский

Citations

9
Next-Generation Immunotherapy for Hepatocellular Carcinoma: Mechanisms of Resistance and Novel Treatment Approaches DOI Open Access
Shabnam Eghbali, Thatcher Heumann

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 236 - 236

Published: Jan. 13, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and, with only 15-20% HCC patients being suitable for potentially curative treatments, the vast majority ultimately require systemic therapy. For decades, choice effective therapy remained sparse. In recent years, after combination atezolizumab and bevacizumab demonstrated superior overall survival over first-line standard, sorafenib, there has been major therapeutic paradigm shift to immunotherapy-based regimens HCC. While representing great leap forward treatment this cancer, reality that less than one-third achieve an objective response immune checkpoint inhibitor-based therapy, so remains significant clinical need further optimization. review, we provide overview current landscape immunotherapy unresectable delve into tumor intrinsic extrinsic mechanisms resistance established immunotherapies focus on novel targets strong translational potential. Following this, spotlight emerging approaches notable trials aiming optimize efficacy in include inhibitors, microenvironment modulators, targeted delivery systems, locoregional interventions.

Language: Английский

Citations

1
Self-assembling chemodrug fiber-hydrogel for transarterial chemoembolization and radiotherapy-enhanced antitumor immunity DOI
Yisheng Peng, Hui Liu,

Xiaoliu Liang

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 1 - 16

Published: Feb. 3, 2025

Language: Английский

Citations

1
Polymeric Nanoparticles Simultaneously Delivering Paclitaxel Prodrug and Combretastatin A4 with Exceptionally High Drug Loading for Cancer Combination Therapy DOI

Huicong Zhou,

Zhaofan Yang,

Guan-Yu Jin

et al.

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Nanomedicines capable of delivering multiple drugs have become essential in combination therapy. However, the challenges low drug loading capacity (DLC) and difficulties administering dosages between different significantly limit antitumor efficacy. In this study, a nanomedicine constructed through rational prodrug nanocarrier design was reported for cancer Initially, phenylborate ester (PBE) group-modified paclitaxel (PTX) (PTX-PBE) synthesized could self-assemble water. Subsequently, combretastatin A4 (CA4) polymer conjugates, mPEG-PCA4 (PCA4), were as nanocarriers to facilitate exceptionally high PTX-PBE precisely controlled manner. Both vitro vivo experiments demonstrated that PCA4 nanoparticles (PCA4/PTX-PBE NPs) exhibited potent efficacy favorable biocompatibility. Our approach provides straightforward, efficient, controllable strategy co-delivery pharmaceuticals clinical

Language: Английский

Citations

1
Immunosenescence and immunotherapy in elderly patients with hepatocellular carcinoma DOI
Dengyong Zhang,

Yan Zhu,

Zhengchao Shen

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: 111, P. 60 - 75

Published: Feb. 26, 2025

Language: Английский

Citations

1
Naringenin: a potential therapeutic agent for modulating angiogenesis and immune response in hepatocellular carcinoma DOI Creative Commons

Wenmei Wu,

Xiangyu Qiu,

Xiaofan Ye

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101254 - 101254

Published: March 1, 2025

Language: Английский

Citations

1