Exploring the role of the immune microenvironment in hepatocellular carcinoma: Implications for immunotherapy and drug resistance DOI Creative Commons
Yumin Fu, Xinyu Guo, Linmao Sun

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Aug. 15, 2024

Hepatocellular carcinoma (HCC), the most common type of liver tumor, is a leading cause cancer-related deaths, and incidence cancer still increasing worldwide. Curative hepatectomy or transplantation only indicated for small population patients with early-stage HCC. However, HCC are not candidates radical resection due to disease progression, choice conventional tyrosine kinase inhibitor drug sorafenib as first-line treatment. In past few years, immunotherapy, mainly immune checkpoint inhibitors (ICIs), has revolutionized clinical strategy Combination therapy ICIs proven more effective than sorafenib, trials have been conducted apply these therapies patients. Despite significant progress in molecular mechanisms behind it remain unclear, resistance often challenging overcome. Several studies pointed out that complex intercellular communication network microenvironment regulates tumor escape response. This underscores urgent need analyze review describes immunosuppressive cell populations HCC, well related trials, aiming provide insights next generation precision immunotherapy.

Language: Английский

Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy DOI Creative Commons
Xiaoting Luo, Xin He, Xingmei Zhang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(2)

Published: Feb. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It regarded as significant public health issue because of its complicated pathophysiology, metastasis, and recurrence rates. There are no obvious symptoms in early stage HCC, which often leads to delays diagnosis. Traditional treatment methods such surgical resection, radiotherapy, chemotherapy, interventional therapies have limited therapeutic effects for HCC patients or metastasis. With development molecular biology immunology, signaling pathways immune checkpoint were identified main mechanism progression. Targeting these molecules has become new direction HCC. At present, combination targeted drugs inhibitors first choice advanced patients. In this review, we mainly focus on cutting‐edge research corresponding therapy immunotherapy great significance comprehensively understand pathogenesis search potential targets, optimize strategies

Language: Английский

Citations

32
Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets DOI Open Access
Greta Pessino, Claudia Scotti, Maristella Maggi

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 901 - 901

Published: Feb. 23, 2024

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, genetic factors. No specific alterations are unequivocally linked to tumorigenesis. Current standard therapies surgical options, systemic chemotherapy, kinase inhibitors, like sorafenib regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint such as atezolizumab pembrolizumab, show efficacy, combination enhance clinical responses. Despite this, the treatment of (HCC) remains challenge, complex tumor ecosystem immunosuppressive microenvironment associated with it hamper efficacy available therapeutic approaches. This review explores current advanced approaches treat HCC, considering both known new potential targets, especially derived from proteomic analysis, which is today considered most approach. Exploring novel strategies, this discusses antibody drug conjugates (ADCs), chimeric antigen receptor T-cell therapy (CAR-T), engineered antibodies. It then reports systematic analysis main ligand/receptor pairs molecular pathways reported be overexpressed cells, highlighting their limitations. Finally, TGFβ, one targets microenvironment.

Language: Английский

Citations

19
Parkin modulates the hepatocellular carcinoma microenvironment by regulating PD-1/PD-L1 signalling DOI Creative Commons

Guiqin Ye,

Xin Sun,

Jiuzhou Li

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Parkin-mediated mitophagy is essential for the clearance of damaged mitochondria, and it inhibits tumour development. The role in modulating immunity becoming clearer, but underlying mechanism still poorly understood.

Language: Английский

Citations

2
POSTN+cancer-associated fibroblasts determine the efficacy of immunotherapy in hepatocellular carcinoma DOI Creative Commons
Hao Wang, Yuan Liang, Zheng Liu

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(7), P. e008721 - e008721

Published: July 1, 2024

Objective Hepatocellular carcinoma (HCC) poses a significant clinical challenge because the long-term benefits of immune checkpoint blockade therapy are limited. A comprehensive understanding mechanisms underlying immunotherapy resistance in HCC is imperative for improving patient prognosis. Design In this study, to systematically investigate characteristics cancer-associated fibroblast (CAF) subsets and dynamic communication among tumor microenvironment (TME) components regulated by CAF subsets, we generated an atlas compiling single-cell RNA sequencing (scRNA-seq) datasets on 220 samples from six datasets. We combined spatial transcriptomics with scRNA-seq multiplexed immunofluorescence identify specific TME that determine efficacy patients. Results Our findings highlight pivotal role POSTN + CAFs as potent response barriers at locations, they hinder effective T-cell infiltration decrease immunotherapy. Additionally, elucidated interplay between SPP1 macrophages, whereby former recruits latter triggers increased expression via IL-6/STAT3 signaling pathway. Moreover, demonstrated correlation revealing immunosuppressive limits response. Notably, found patients elevated levels both macrophages achieved less therapeutic benefit cohort. Conclusion research elucidates light particular subset resistance, emphasizing potential targeting subpopulations improve responses

Language: Английский

Citations

13
Increased Siglec-9/Siglec-9L interactions on NK cells predict poor HCC prognosis and present a targetable checkpoint for immunotherapy DOI
Rong Xiao, Ye Tian, Jiwei Zhang

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(5), P. 792 - 804

Published: Feb. 7, 2024

Language: Английский

Citations

12
Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis DOI
Xinpei Li,

Shijie Shang,

Meng Wu

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217096 - 217096

Published: July 4, 2024

Language: Английский

Citations

11
Small-molecule-based targeted therapy in liver cancer DOI
Ming Yue, Yanqiu Gong,

Xuewen Fu

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(10), P. 3260 - 3287

Published: Aug. 8, 2024

Language: Английский

Citations

11
Hepatic stellate cells promote hepatocellular carcinoma development by regulating histone lactylation: novel insights from single-cell RNA sequencing and spatial transcriptomics analyses DOI

Yifan Yu,

Yongnan Li, Long Zhou

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: unknown, P. 217243 - 217243

Published: Sept. 1, 2024

Language: Английский

Citations

9
Utilizing liquid-liquid biopolymer regulators to predict the prognosis and drug sensitivity of hepatocellular carcinoma DOI Creative Commons
Jianhao Li, Han Chen, Lang Bai

et al.

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 6, 2025

Liquid-liquid phase separation (LLPS) is essential for the formation of membraneless organelles and significantly influences cellular compartmentalization, chromatin remodeling, gene regulation. Previous research has highlighted critical function liquid-liquid biopolymers in development hepatocellular carcinoma (HCC). This study conducted a comprehensive review 3,685 biopolymer regulators, leading to LLPS related Prognostic Risk Score (LPRS) HCC through bootstrap-based univariate Cox, Random Survival Forest (RSF), LASSO analyses. A prognostic nomogram patients was developed using LPRS other clinicopathological factors. We utilized SurvSHAP identify key genes within influencing prognosis. To validate our findings, we collected 49 cases along with adjacent tissue samples confirmed correlation between DCAF13 expression progression qRT-PCR analysis vitro experiments. established 8 LLPS-related (TXN, CBX2, DCAF13, SLC2A1, KPNA2, FTCD, MAPT, SAC3D1). Further indicated that high closely associated vascular invasion, histological grade (G3-G4), TNM stage (III-IV) HCC, concurrently establishing as an independent risk factor integrates staging patient age markedly improves predictive accuracy survival outcomes patients. Our findings suggest increased plays crucial role cancer angiogenesis. Navitoclax emerged promising treatment levels, offering novel therapeutic direction by targeting LLPS. have formulated model capable accurately predicting clinical prognosis drug sensitivity HCC. might play pivotal malignant mediated

Language: Английский

Citations

1
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