Liver fibrosis, marked by excessive deposition of extracellular matrix (ECM), is a critical precursor to cirrhosis, liver failure, and hepatocellular carcinoma. Accumulating evidence highlights that cellular senescence, characterized by stable cell-cycle arrest and the senescence-associated secretory phenotypes (SASPs), is a key regulator of the fibrotic process. This review systematically dissects the context-dependent roles of senescent cells in liver fibrosis, with a focus on hepatocytes, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells, and natural killer (NK) cells. Distinct populations of senescent cells emerge sequentially during different stages of fibrosis, exhibiting divergent kinetics and functional effects. The SASP, a dynamic cocktail composed of cytokines, chemokines, and proteases, remodels the intrahepatic microenvironment through immune cell recruitment, regulation of cell function, and modulation of ECM turnover. These effects vary depending on their molecular composition and disease context. Furthermore, we discuss emerging senescence-targeted therapeutic strategies to restore liver homeostasis. In-depth understanding of the cell-type and stage-specific roles of senescence in fibrosis provides a molecular foundation for translating senescence-targeted strategies into clinical precision antifibrotic therapies.
Cirrhosis, characterized by extensive liver fibrosis and architectural distortion, is commonly associated with coagulation disorders that increase the risk of both bleeding and thrombosis. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy for liver diseases, including cirrhosis, due to their regenerative and immunomodulatory properties. This review delves into the intricate relationship between MSCs and the coagulation system in cirrhotic patients, examining the impact on platelet dysfunction, coagulation factor synthesis, endothelial dysfunction, and fibrinolysis. The review highlights MSCs’ multilineage differentiation potential and their ability to secrete both pro- and anti-coagulant factors, which are crucial in the context of liver disease. Clinical and preclinical findings on the effects of MSC therapy on coagulation are reviewed, along with safety and risk assessments. This review highlights the promising potential of MSCs in alleviating cirrhosis-associated coagulopathy, while identifying key challenges that must be addressed to advance clinical translation. Further research is therefore warranted to elucidate the underlying mechanisms and to optimize therapeutic strategies for clinical application.
Background and aims Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, highlighting the urgent need to identify novel therapeutic targets. Bioinformatic analysis initially identified meiotic nuclear division 1 (MND1) as a differentially expressed gene in HCC, with significant associations to DNA damage repair pathways, suggesting its potential functional relevance in hepatocarcinogenesis. Based on these findings, this study aims to systematically characterize the expression profile of MND1 in HCC and to further elucidate its biological functions as well as the underlying molecular mechanisms driving HCC progression. Methods The expression profile of MND1 was validated using data from public databases along with 22 paired clinical HCC specimens. The functional roles of MND1 were investigated through in vitro assays (CCK-8, Transwell, and flow cytometry) and in vivo subcutaneous/orthotopic xenograft mouse models. Mechanistically, co-immunoprecipitation (Co-IP) coupled with mass spectrometry, immunofluorescence, and rescue experiments were applied to identify interacting proteins and to elucidate the underlying molecular pathways. Results Multi-omics analysis and clinical validation revealed that MND1 is overexpressed in HCC tissues and significantly correlates with poor prognosis. Comprehensive in vitro and in vivo functional studies further demonstrated that MND1 drives HCC progression by regulating tumor cell proliferation, migration, and invasion. Mechanistically, we uncovered a close functional association between MND1 and TRIM28, which promotes genomic instability by enhancing the activity of the DNA damage response (DDR) pathway. Conclusions These findings suggest that MND1 may serve as both a potential molecular marker and an oncogenic contributor in HCC. Importantly, the newly identified MND1–TRIM28–DDR regulatory axis offers a promising rationale for the development of targeted therapeutic strategies.
Background and aims Liver cancer remains a major global health burden with a complex and shifting epidemiology. While viral hepatitis continues to drive significant morbidity, metabolic risk factors are increasingly contributing to the incidence of liver cancer. Utilizing data from the Global Burden of Disease (GBD) Study 2021, this analysis examines China's incidence, prevalence, and age-standardized disability-adjusted life year (DALY) rates for liver cancer from 1990 to 2021, comparing these trajectories against global and regional patterns. This study further analyzed the correlations between liver cancer burden and socioeconomic development, aiming to provide evidence for targeted intervention strategies and health policy formulation. Methods This study utilized data from the Global Burden of Disease Study 2021 to analyze the burden of liver cancer from 1990 to 2021 across 204 countries and territories. Standardized methodologies were used to estimate prevalence, incidence and DALYs. The Socio-demographic index (SDI) was applied to evaluate Socioeconomic disparities. Joinpoint regression was employed to analyze temporal trends, and age-period-cohort modeling was applied to estimate drivers of disease burden. Age-standardized rates were projected to 2035 using statistical modeling techniques. Results Globally, the absolute number of liver cancer increased continously, wherea age-standardized rates declined from 1990 to 2021. Prevalent cases increased by 113.7% (from 345,912.7 to 739,299.5), incident cases increased by 116.2% (from 244,689.4 to 529,202.5), and total DALYs grew by 70.6% (from 7,553,666.8 to 12,887,652.4); the age-standardized DALY rate (ASDR) declined with an estimated annual percentage change (EAPC) of –0.6 (95% CI –0.72 to –0.48). Hepatitis B-related DALYs decreased significantly, while non-alcoholic steatohepatitis (NASH) and alcohol-related cases increased. China achieved marked reductions in age-standardized rates: the age-standardized incidence rate (ASIR) decreased from 10.6 to 9.5 per 100,000 (EAPC –0.28, 95% CI –0.42 to –0.13), and the ASDR fell from 334.5 to 239.9 per 100,000 (EAPC –1.16, 95% CI –1.34 to –0.98), especially in hepatitis B, though metabolic-related burdens grew. Prevalent cases in China doubled (from 132,779.2 to 265,539.4) and incident cases rose by 104.0% (from 96,434.3 to 196,636.6). Gender and age disparities were evident, with males and older adults bearing higher burdens. High-income regions saw rising metabolic-related rates, whereas low- and middle-income areas faced persistent viral hepatitis burdens. Projections suggest a continued rise in metabolic-related liver cancer globally, with NASH-related rates accelerating fastest in China, underscoring the need for dual preventive strategies targeting both infection and lifestyle factors. Conclusions The global burden of liver cancer is undergoing an epidemiological transition, marked by declining viral hepatitis-related rates but rising metabolic and alcohol-related cases. Significant reductions in age-standardized rates were observed in China, though absolute cases increased. Socioeconomic and geographic disparities persist, with high-income regions facing growing metabolic burdens. Future trends emphasize the need for integrated strategies addressing both infectious and lifestyle-related risk factors.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disorder worldwide, characterized by complex molecular regulatory networks driving its pathogenesis. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), serve as critical regulators of gene expression and have been increasingly recognized for their pivotal roles in MASLD development. Rather than functioning in isolation, these ncRNAs form intricate regulatory networks that integrate and amplify disease signals across multiple cellular compartments and pathological stages. This review provides a comprehensive overview of how these ncRNA networks orchestrate MASLD progression, focusing on their roles in metabolic dysregulation, inflammation, and fibrosis. We further evaluate the diagnostic potential of circulating ncRNAs as stable, non-invasive biomarkers for disease stratification and monitoring, and discuss emerging therapeutic strategies targeting ncRNAs, including antisense oligonucleotides, synthetic mimics, and advanced delivery platforms such as lipid nanoparticles and engineered exosomes. Despite significant progress, challenges related to delivery efficiency, tissue specificity, and safety remain barriers to clinical translation. By synthesizing current knowledge of ncRNA networks in MASLD and highlighting opportunities for therapeutic intervention, this review provides a roadmap for translating ncRNAs into clinical applications for this increasingly prevalent metabolic liver disease.
Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.
Background and aims:Hepatocellular carcinoma (HCC) cells are metabolically reprogrammed for excessive uptake and metabolism of many nutrients. The tumor suppressive microRNA-148a-3p (miR-148a-3p) is downregulated in HCC, whereas its function in regulating HCC cell metabolism remains obscure. Herein we aimed to delineate the role of miR-148a-3p in HCC cell metabolism by using novel bioengineered miR-148a-3p (BioRNALeu/miR-148a-3p) agent produced in vivo. Methods:BioRNALeu/miR-148a-3p was designed by using human leucyl transfer RNA fused hsa-pre-miR-34a carrier, overexpressed in Escherichia coli (E. coli), and purified to high homogeneity. After transfection into HCC cells, the released miR-148a-3p levels were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by CellTiter-Glo assays. Targets were validated by dual-luciferase reporter assays, immunoblotting, and immunofluorescence confocal imaging. Glycolysis capacity was evaluated by Seahorse XF assays, and glucose, lactate, and amino acid levels were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Results:BioRNALeu/miR-148a-3p was efficiently processed into target miR-148a-3p in HCC cells to effectively inhibit cell proliferation in a dose- and time-dependent manner. Mechanistically, miR-148a-3p suppressed the protein levels of glucose transporter GLUT1/SLC2A1 and L-type amino acid transporter LAT1/SLC7A5 via acting on their 3'-untranslated regions, as well as amino acid transporter ASCT2/SLC1A5. These, in turn, led to a reduction of glucose uptake, lactate production, and glycolytic flux in HCC cells, and alteration of intracellular amino acid metabolome including glutamine, leucine, phenylalanine, tyrosine, and methionine. Conclusions:Reintroduction of miR-148a-3p into HCC cells modulates glucose and amino acid metabolism via regulating multiple SLC transporters, thereby suppressing HCC cell viability. These findings highlight the role of miR-148a-3p in HCC cell metabolism and potential of bioengineered miRNA molecules for functional studies and therapeutic development.
As the central metabolic organ, the liver coordinates fundamental biological processes through its specialized cellular architecture and regulatory networks, encompassing metabolism, immunity, and regeneration. Kupffer cells (KCs), the liver-resident macrophages, exhibit functional heterogeneity beyond classical polarization paradigms. Currently, multiple classification systems for KCs have been established utilizing distinct surface markers. However, there is no systematic theoretical framework for the classification of KCs. The strategic positioning of KCs within the hepatic Disse space enables intricate intercellular communication networks with neighboring hepatocytes for coordinated physiological regulation. Their functional plasticity critically regulates systemic iron and metabolic homeostasis, with KC-driven metabolic reprogramming directly influencing hepatic pathophysiology. Furtherly, KC activity shows spatiotemporal regulation by circadian rhythms and nutrient signals, reshaping the liver microenvironment to affect function. This review summarizes advances in liver macrophage biology, highlighting the classification challenges of KCs and their roles in hepatic physiology. Additionally, we discuss how circadian rhythms, aging, diet, and exercise dynamically influence KC functionality, which provides a framework to interpret their regulatory logic and dysfunction in disease.
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.
Bile acids (BAs) serve not only as key facilitators of lipid absorption but also as crucial signaling molecules regulating glucose and lipid metabolism, inflammation, and overall energy homeostasis. Aging profoundly alters BA metabolism, characterized by shifts in biosynthetic pathways, compositional changes, disrupted receptor-mediated signaling, and alterations in gut microbiota interactions. These age-related changes contribute to the onset and progression of metabolic conditions, including type 2 diabetes, obesity, metabolic dysfunction-associated fatty liver disease, and neurodegenerative disorders. An increased abundance of hydrophobic and cytotoxic BAs has been associated with systemic inflammation, metabolic rigidity (disruption of metabolic flexibility), and organ dysfunction. Targeting BA signaling—through pharmacological modulation of farnesoid X receptor and Takeda G protein-coupled receptor 5 or microbiota-directed therapies—offers promising strategies to mitigate aging-related metabolic decline. A deeper understanding of how BA metabolism evolves over the lifespan may unveil novel interventions to promote healthy aging and prevent age-related disease.
End-stage liver disease (ESLD) covers the end-stage of acute and chronic liver diseases, mainly involving decompensated cirrhosis, various types of liver failure, and advanced liver cancer. Hepatocyte transplantation has shown promise in treating ESLD, but its clinical application is hampered by the shortage of donor hepatocytes. Cell therapy, an emerging effective treatment for ESLD, faces the same limitation due to scarce hepatocyte availability. Hepatocyte-like cells (HLCs), which are terminally differentiated cells, can be induced from both stem cells and somatic cells. As HLCs exhibit the morphology and function of primary hepatocytes, they offer a promising supplementary source of hepatocytes for cell therapy. First, we provide a background for the differentiation and maturation of primary hepatocytes. Subsequently, based on the current insights into the molecular pathways that regulate hepatocyte differentiation in vivo, we describe a strategy for establishing HLC derived from either stem cells or somatic cells. The key characteristics of these HLCs are also detailed. Furthermore, HLC offers therapeutic potential for liver failure, and HLC-based liver organoids and bioartificial liver systems have demonstrated the ability to provide liver functions, offering an innovative approach to treating various types of ESLD. Despite their promise, challenges such as efficiency in differentiation and functional maturation need to be addressed to improve the clinical application of HLCs. This review discusses these advancements and outlines the therapeutic potential and current challenges of HLC therapy for ESLD.
Background and aims Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide, with no currently effective treatment. ALD is caused by excessive lipid buildup, which eventually triggers inflammation and fibrosis in the liver. Activation of hepatic Kupffer cells (KCs) and macrophages drives liver inflammation, which can worsen alcohol-induced liver injury. The autophagy-lysosome system is crucial for macrophages to support their innate immune functions. Transcription factor EB (TFEB) is a key regulator of autophagy and lysosomal biogenesis, but the role of macrophage TFEB in ALD development is unknown. The aim of this study was to evaluate the effects of Gao-binge alcohol consumption on myeloid cell TFEB and elucidate the role of myeloid TFEB in ALD. Methods Two-to-three-month old male and female LysM Cre- (WT) and LysM Cre+ Tfeb Flox/Flox (f/f) (myeloid-Tfeb KO) mice were subjected to chronic alcohol feeding plus an acute binge following the Gao-binge model. Serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol content were determined using biochemical assays. Total hepatic protein content and messenger RNA (mRNA) levels of autophagy-related proteins and inflammatory markers were determined using immunoblotting, immunohistochemistry, and real-time quantitative polymerase chain reaction (RT-qPCR). Isolated hepatic infiltrating macrophages and KCs from mice given intragastric ethanol infusions were analyzed by Western blot for TFEB and autophagy-related protein content. Raw 264.7 macrophages were treated with ethanol, lipopolysaccharide (LPS), and LPS plus ethanol to examine nuclear TFEB translocation using immunofluorescence. Results We found that TFEB levels were higher in macrophage/KC cells than in hepatocytes and cholangiocytes. While ethanol feeding increased serum alanine aminotransferase and aspartate aminotransferase levels, as well as hepatic triglyceride levels, no significant differences were observed between WT and myeloid-Tfeb KO mice. The number of F4/80-positive KCs/macrophages was similar in all four experimental groups, but hepatic neutrophil infiltration increased in alcohol-fed myeloid- Tfeb KO mice. LPS or ethanol alone induced nuclear TFEB translocation only moderately in Raw 264.7 macrophages. Conclusions Our findings suggest that myeloid TFEB is dispensable for alcohol-induced liver injury in mice.
Cholangiocarcinoma (CCA) is a malignancy characterized by tumor cells originating in the liver or bile ducts, exhibiting features of cholangiocyte differentiation. It poses a significant clinical challenge due to the limited diagnostic and therapeutic options available. Robust animal models are essential for advancing our understanding of CCA pathogenesis and developing effective treatments. This review provides a comprehensive overview of CCA mouse models, highlighting various approaches, including chemical induction, genetically engineered models, and tumor xenografts. Each model is discussed in terms of its establishment techniques, pathological characteristics, and research significance, with a focus on intrahepatic CCA. Chemical induction models, such as diethylnitrosamine- and azoxymethane-induced models, offer insights into tumorigenesis processes, whereas genetically modified models involving alterations in key genes such as Kirsten rat sarcoma viral oncogene homolog, tumor protein 53, and isocitrate dehydrogenase serve as important tools for studying the molecular mechanisms underlying CCA. Xenograft models, including patient-derived xenografts, bridge the gap between experimental research and clinical applications, allowing for precise therapeutic evaluations. By comparing these models, this review underscores their respective advantages and limitations, paving the way for future studies aiming to optimize and innovate CCA modeling strategies.
Liver cirrhosis, an advanced end-stage liver disease characterized by extensive hepatic fibrosis, is a leading cause of mortality and morbidity worldwide. Despite its prevalence, there is no specific treatment to prevent fibrosis progression, with liver transplantation remaining the only definitive option for patients with advanced cirrhotic liver disease. The activation of hepatic stellate cells (HSCs) by proinflammatory M1-type Kupffer cells (KCs) is a key driver of fibrosis. Activated HSCs further exacerbate fibrosis by recruiting bone marrow-derived macrophages (BMDMs) through chemokine signaling, which induces alpha-smooth muscle actin (alpha-SMA) expression. Autophagy, a cellular process responsible for degrading damaged organelles and protein aggregates, is vital for maintaining liver physiology and metabolic balance. It also plays a significant role in the pathogenesis of fibrosis. Compounds that promote KC autophagy can polarize KCs toward an anti-inflammatory M2 phenotype, disrupting signaling pathways that activate HSCs and recruit BMDMs to injured liver tissue. This approach has been identified as a promising therapeutic strategy to combat liver fibrosis. This review highlights various strategies to activate KC autophagy and modulate KC polarization, offering insights into novel therapeutic targets for treating liver fibrosis and preventing cirrhosis progression.
Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.
Yttrium-90 microsphere selective internal radiation therapy (SIRT), also known as transarterial radioembolization, has become one of the pivotal treatments for liver cancer, particularly for selected advantageous patient groups. This review summarizes the characteristics of different patients with liver cancer that could obtain maximum benefit from SIRT and discusses key factors affecting efficacy and safety, including tumor characteristics, liver function, patient performance status, and treatment intent. In evaluating appropriate candidates, mapping serves as a crucial simulation procedure to assess tumor vascular anatomy, predict lung shunting, and guide catheter positioning and dose planning. This procedure substantially enhances therapeutic precision while minimizing the risk of nontarget radiation-related adverse events, such as radiation-induced pneumonitis and gastrointestinal toxicity. Several studies have suggested that SIRT is not only suitable for patients with early or limited hepatocellular carcinoma but can also be used as a bridging therapy for liver transplantation and conversion therapy for unresectable liver cancers. In combination with systemic treatments, SIRT has demonstrated survival benefits in patients with unresectable liver cancer. This review also highlights the importance of further optimizing patient screening through personalized dosimetry and mapping to ensure the precision and safety of treatment. A thorough review of relevant literature and clinical practice offers clinicians comprehensive suggestions on patient screening and clarifies the promise of SIRT in the liver cancer population.
Lactic acidosis is a hallmark of the tumor microenvironment (TME) and a critical impediment to the efficacy of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Incomplete embolization preserves viable tumor cells that amplify hypoxia-driven glycolysis, generating a lactic acid-rich milieu that drives treatment resistance, skews immune populations toward immunosuppressive phenotypes, and impairs cytotoxic T lymphocyte function. In this review, we elucidate the pathways through which lactic acidosis compromises TACE efficacy and propose novel strategies for its mitigation. We examine emerging approaches, including systemic or intra-arterial alkalization, targeted inhibition of lactate production and export, and calcium carbonate nanoparticles, and evaluate their respective merits and limitations. Finally, we propose a combination regimen of calcium carbonate nanoparticles, lactate-targeting agents, and TACE to achieve precise drug delivery, synergistic lactic acid depletion, and enhanced antitumor immunity. These integrated strategies have the potential to convert immunologically “cold” HCC lesions into “hot” ones, thereby improving TACE outcomes and disease control.
