Liver Cancer最新文献

{"title":"Spatiotemporal, Statistical, and Anatomical Considerations for Translating Multi-Omics Cholangiocarcinoma Subtypes into Immunotherapy Biomarkers","authors":"Shiyuan Li,Meng Xia","doi":"10.1159/lic/admag024","DOIUrl":"https://doi.org/10.1159/lic/admag024","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quavonlimab Coformulated With Pembrolizumab Plus Lenvatinib for Advanced Hepatocellular Carcinoma: Nonrandomized Phase 2 KEYSTEP-004 Trial","authors":"Daneng Li,Lorenza Rimassa,Masafumi Ikeda,Mark Yarchoan,Baek-Yeol Ryoo,Thibaud Koessler,Ho Yeong Lim,Mariusz Kwiatkowski,Ting-Tsung Chang,Jee Hyun Kim,Andrea Casadei Gardini,Masatoshi Kudo,ZhengGang Ren,Maria Varela,Josep M Llovet,Razi Ghori,Ken Hatogai,Abby B Siegel,Ann-Lii Cheng","doi":"10.1159/lic/admag013","DOIUrl":"https://doi.org/10.1159/lic/admag013","url":null,"abstract":"Introduction: Despite the availability of several approved therapies, continued investigation of novel treatment options is needed to further improve outcomes in advanced hepatocellular carcinoma (HCC). The phase 2 KEYSTEP-004 study evaluated safety and efficacy of quavonlimab coformulated with pembrolizumab (quavonlimab/pembrolizumab) plus lenvatinib as first-line therapy for advanced HCC. Methods: Adults with confirmed advanced HCC and no prior systemic therapy were enrolled. In the safety lead-in phase, participants received intravenous quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks plus oral lenvatinib 12 mg (body weight ≥60 kg) or 8 mg (body weight <60 kg) once daily (dose level 0 [DL0]). Allocation to the efficacy expansion phase was permitted if lenvatinib DL0 plus quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks was determined to be tolerable. Primary end points were objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR) and safety. Secondary end points included duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, and overall survival (OS). Results: As of June 22, 2023, 116 participants were enrolled and 115 were treated. No dose-limiting toxicities were observed in the safety lead-in phase. Lenvatinib DL0 in combination with quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks was determined to be tolerable. Median study follow-up was 18.0 months (range, 12.0-26.6). Confirmed ORR was 37.4% (95% CI, 28.5-46.9). Median DOR was 10.6 months (range, 1.2+ to 23.1+), median PFS was 8.2 months (95% CI, 6.2-10.2), and median OS was 22.1 months (95% CI, 15.5-not reached). Grade 3-5 treatment-related adverse events (AEs) occurred in 66 participants (57.4%); 14 (12.8%) required high-dose steroids for management of a treatment-related AE. Conclusion: Quavonlimab coformulated with pembrolizumab plus lenvatinib is an active combination and has a manageable safety profile in advanced HCC.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"36 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary cholesterol promotes MASLD-related hepatocellular carcinoma through mitochondrial dysfunction","authors":"Xiaoming Zhang,Xingyu Zhou,Xiangtian Yu,Chuanfa Liu,Zhongjun Feng,Eagle SH Chu,Harry Cheuk-Hay Lau,Jiandong Zhang,Xiaoyan Bian,Tao Zeng,Xiang Zhang","doi":"10.1159/lic/admag023","DOIUrl":"https://doi.org/10.1159/lic/admag023","url":null,"abstract":"Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent disease that can progress to hepatocellular carcinoma (HCC). Excess dietary cholesterol is associated with MASLD-HCC, but its role in liver malignancy remains unclear. Here, we aimed to investigate the mechanism of how dietary cholesterol promotes MASLD-HCC. Methods: C57BL/6 mice were fed with high-cholesterol (HC) or low-cholesterol (LC) diet for 14 months. Mouse liver tissues were subjected to transcriptome, whole-exome, and methylation sequencing. Cholesterol-lowering atorvastatin was used for intervention experiment. Mitochondrial function was assessed in mouse liver tissues and human MASLD-HCC cell lines. Plasma samples from 88 hypercholesteremia patients and 88 healthy individuals were collected. Results: Liver tumors were observed in HC-fed mice, and mitochondrial dysfunction was identified as the key pathway in cholesterol-induced MASLD-HCC. In particular, impaired mitochondrial function and reduced mitochondrial membrane potential and integrity were observed in the liver of HC-fed mice. Pten was the central gene associated with mitochondrial dysfunction in cholesterol-induced MASLD-HCC. Cholesterol also dysregulated mitochondrial function and promoted proliferation of human MASLD-HCC cells, whereas the pro-proliferative effect of cholesterol was reversed after pharmacological restoration of mitochondrial function. Similarly, atorvastatin treatment could restore mitochondrial function and increase Pten expression in HC-fed mice, thereby inhibiting MASLD-HCC development. Mechanistically, mitochondrial dysfunction in MASLD-HCC was caused by hypermethylation of mitochondria-associated genes. Hypercholesterolemia patients exhibited features of mitochondrial dysfunction, compared to healthy controls. Conclusion: Dietary cholesterol promotes MASLD-HCC by inducing methylation-mediated mitochondrial dysfunction and PTEN loss. Restoring mitochondrial function and cholesterol-lowering drugs might serve as potential therapeutics for MASLD-HCC.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"44 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of achieving a tumor- and drug-free state through conversion therapy followed by curative hepatectomy for patients with initially unresectable hepatocellular carcinoma (GUIDANCE009)","authors":"Da-Long Yang,Yong-Rong Liang,Ze Su,Teng-Xian Zhou,Zhi-Cheng Li,Ming-Song Wu,Xue-Yao Wang,Hong-Bing Yao,Shao-Ping Liu,Jun-Liang Nong,Pei-Sheng Wu,Chuang Qin,Zhen Liu,Shu-Chang Chen,Jun-jie Ou,Teng-Meng Zhong,Yi-He Yan,Kang Chen,Zhi-Hao Huang,Lei-Po Lin,Yi-Li Ma,Liang Ma,Jian-Hong Zhong","doi":"10.1159/lic/admag021","DOIUrl":"https://doi.org/10.1159/lic/admag021","url":null,"abstract":"Background: Whether initially unresectable hepatocellular carcinoma (HCC) patients who receive curative resection after conversion therapy can maintain long-term tumor-free survival in a drug-free state after postoperative drug withdrawal is unclear. This study aimed to compare the effectiveness of adjuvant PD-1 inhibitors versus a drug-free state in these patients. Methods: Data were retrospectively analyzed for patients with initially unresectable HCC who underwent curative hepatectomy after conversion therapy at 13 medical centers in China between January 2019 and June 2023. Tumor-free survival (TFS) and overall survival (OS) were compared between patients who received PD-1 inhibitors and patients in a drug-free state after hepatectomy. Results: Relative to the 311 patients in a drug-free state, the 114 who received PD-1 inhibitors showed comparable TFS (HR 0.85, 95%CI 0.63-1.15) and OS (HR 0.66, 95%CI 0.44-1.00). Similar results were obtained for subsets of patients matched to each other through propensity scoring, for the subset of 123 patients who achieved pathological complete response after resection, and for the entire cohort in 12-month landmark survival analysis. An adjuvant PD-1 inhibitor regimen lasting at least 6 months led to similar survival as shorter regimens, whether in terms of TFS (HR 0.61, 95% CI 0.35-1.04) or OS (HR 0.51, 95% CI 0.22-1.19). Multivariable analyses identified multiple tumors, tumor satellites, and absence of pathological complete response as independent adverse predictors of impaired TFS and OS; albumin-bilirubin grade 2 independently predicted inferior TFS only. No treatment-related deaths occurred in the entire cohort. Conclusions: We failed to demonstrate a survival benefit of adjuvant PD-1 inhibitors compared with drug-free state in patients with initially unresectable HCC who underwent curative hepatectomy after conversion therapy. Given the relatively short follow-up, small sample size, and retrospective design, these findings should be need further validation in prospective randomized controlled trials.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"1 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transarterial Chemoembolization Combined with Immunotherapy-Based Systemic Therapy for Hepatocellular Carcinoma: An International ISMIO Expert Consensus Framework","authors":"Bin-Yan Zhong,David Madoff,Arndt Vogel,Xuefeng Kan,Stephen L Chan,David J. Pinato,Yasuaki Arai,Julius Chapiro,Hai-Dong Zhu,Zhenwei Peng,Zhong-Zhi Jia,Peter Galle,Takeshi Okamoto,Kelvin Hong,Jon C Davidson,Aichi Chien,Chu Hui Zeng,Richard Finn,Masatoshi Kudo,Dong Xu,Gao-Jun Teng","doi":"10.1159/lic/admag022","DOIUrl":"https://doi.org/10.1159/lic/admag022","url":null,"abstract":"The combination of transarterial chemoembolization (TACE) with immunotherapy-based systemic therapy is emerging as a promising treatment strategy for unresectable hepatocellular carcinoma (HCC). In addition, emerging data from perioperative immunotherapy-based strategies in resectable, high-risk HCC further support the integration of systemic and TACE across the disease continuum. Recent randomized trials have demonstrated improvements in progression-related outcomes with TACE combined with immunotherapy-based systemic therapies. However, overall survival (OS) benefit has not been consistently demonstrated across randomized studies, with final OS analyses from EMERALD-1 and interim OS analyses from LEAP-012 not showing statistically significant improvement compared with TACE alone. By integrating TACE and immunotherapy-based systemic strategies, this International Society of Multidisciplinary Interventional Oncology (ISMIO) Expert Consensus framework does not advocate routine clinical adoption but aims to provide a structured framework for research design and multidisciplinary decision-making. It summarizes data from pivotal trials and offers guidance on patient selection, treatment sequencing, response evaluation, and safety management. Ten consensus statements through a modified Delphi process, with evidence graded according to the Oxford Centre for Evidence-based Medicine and assessed narratively based on the directness, consistency, maturity, and applicability of available evidence, were developed by ISMIO expert panel. The consensus framework emphasizes multidisciplinary collaboration, individualized therapeutic decision-making based on a comprehensive patient profile, and the need for structured definitions and endpoints to facilitate future research. It aims to provide a flexible, evidence-informed, multidisciplinary framework to facilitate patient stratification, interpretation of emerging evidence, and future research design, while allowing adaptation according to local expertise, treatment availability, and regional practice patterns.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"93 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Cells Contribute to the Immune-Vascular Mileu Characterizing VETC+ HCC","authors":"Barbara Durante,Simone Zanella,Francesco de Napoli,Beatrice Esposito,Camilla De Carlo,Reha Akpinar,Cristina Richichi,Francesca Lazzaroni,Barbara Franceschini,Cristiana Soldani,Fabio Grizzi,Fabio Pasqualini,Ana Lleo,Guido Torzilli,Fabio Procopio,Luca Viganò,Salvatore Piscuoglio,Charlotte K Y Ng,Federica Airi,Elvezia Paraboschi,Ines Simeone,Luca Di Tommaso","doi":"10.1159/lic/admag014","DOIUrl":"https://doi.org/10.1159/lic/admag014","url":null,"abstract":"Background. Vessel Encapsulating Tumor Cluster (VETC) defines a distinct vascular phenotype of hepatocellular carcinoma (HCC), characterized by tumor nests fully encased within a continuous endothelial lining. This architecture correlates with poor prognosis and enhanced sensitivity to anti angiogenic therapies. Aim. To dissect the morphological, phenotypical, molecular, and functional programs that define VETC-associated ECs in HCC and to identify endothelial pathways potentially driving VETC vascular organization and tumor progression. Materials and Methods. Biological samples (blood, plasma, PBMCs, and tissue) were collected from VETC+ and VETC– HCCs. Quantitative tissue imaging was integrated with EC-specific molecular profiling. Vascular architecture was assessed on whole-slide images, and purified tumor ECs underwent targeted and transcriptome-wide gene expression analyses. Results. ECs from both VETC+ and VETC– HCCs lacked pro-growth and anti-apoptotic features. VETC+ ECs show overexpression of pro-angiogenic and immune-modulatory factors, in particular VEGFA, FGF and IL10, and a specific gene signature involved in metabolic reprogramming, increased trafficking and migratory capacity. VETC+ transcriptional phenotype is driven by a coordinated hepatic xenobiotic-sensing network in which HNF4A and HNF1A provide the dominant regulatory architecture, while NFE2L2 contributes a distinct regulatory layer governing the ARE-dependent arm of the xenobiotic and oxidative-stress response. Conclusions. VETC+ ECs actively shape the HCC microenvironment through the release of angiogenic and immunomodulatory cues. These findings support the existence of a specialized angiocrine program in VETC+ HCC.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"36 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transjugular Intrahepatic Portosystemic Shunt Promotes Hepatocellular Carcinoma Growth in Metabolic Dysfunction Associated Liver Disease","authors":"Sofia El Hajji,Stéphanie Lacotte,Andrea Peloso,Florence Slits,Charles-Henri Wassmer,Beat Moeckli,Roqiya Bouguerra,Petru Bucur,Fanny Dujardin,Louis D'Alteroche,Laure Elkrief,Christian Toso","doi":"10.1159/lic/admag017","DOIUrl":"https://doi.org/10.1159/lic/admag017","url":null,"abstract":"Introduction: Transjugular intrahepatic portosystemic shunt (TIPS) is validated procedure to alleviate portal hypertension. However, its impact on hepatocellular carcinoma (HCC) remains poorly understood and its potential role in modulating tumor growth is debated. Methods: We performed bulk RNA sequencing of HCC samples from 34 patients with (n=17) and without (n=17) TIPS to identify transcriptional changes associated with shunting. Murine models of diethylnitrosamine (DEN)-induced HCC with surgically induced portosystemic shunt (PSS) were established under either normal diet (ND) or high-fat diet (HFD) to assess molecular and phenotypic effects of PSS in different metabolic contexts. Clinical validation was conducted using the Scientific Registry of Transplant Recipients (SRTR), comparing propensity score-matched MASH-related cirrhosis patients (n=913) with and without TIPS. Results: HCC nodules sequencing showed that TIPS is associated with a positive enrichment of immune-related pathways, without significant changes in immune cell composition. Five differentially expressed genes were upregulated, including coding genes FABP4, GCK, and FOSB which are correlated with improved survival in an independent dataset. ND mice with shunt did not show any difference in growth or carcinogenesis compared to controls. In contrast, HFD mice with shunts showed larger and faster growing HCCs (1.14 vs 0.22 mm3/week, p<0.001) with transcriptomic enrichment of metabolic and proliferative programs. In MASH patients from the SRTR, TIPS was also associated with larger and faster growing HCC (0.20 vs -0.47 cm3/month, p=0.004) consistent with preclinical data. Conclusion: TIPS leads to diverging effects on HCC depending on the underlying metabolic context: immunostimulatory in non-MASLD and tumor-promoting in MASLD. These results warrant further validation but suggest that the use of TIPS in MASLD-related HCC patients should be monitored carefully.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"27 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unexpected Limited Immune Potentiation of Common Multikinase Inhibitors Combined with Immune Checkpoint Blockade in HCC: Insights from Murine Models","authors":"Ying-Chun Shen,Chia-Lang Hsu,Ching-Ping Yeh,Wan-Ying Lin,Yi-Ting Liu,Ann-Lii Cheng","doi":"10.1159/lic/admag016","DOIUrl":"https://doi.org/10.1159/lic/admag016","url":null,"abstract":"Introduction: Blockade of vascular endothelial growth factor (VEGF) signaling can normalize tumor vasculature and enhance antitumor immunity, as exemplified by atezolizumab plus bevacizumab in hepatocellular carcinoma (HCC). VEGF receptor (VEGFR)-targeting multikinase inhibitors (MKIs) have therefore been considered superior partners for immune checkpoint inhibitors (ICIs) because of their broader inhibition of potentially immune-potentiating kinases. However, most MKI–ICI combinations have shown limited clinical benefit. We hypothesized that MKIs may induce additional biological perturbations beyond VEGFR inhibition that counterbalance immune potentiation. Methods: Murine HCC models (Hepa1-6 and Hep53.4) were treated with a selective anti-VEGFR2 antibody (DC101) or VEGFR-targeting MKIs (cabozantinib, lenvatinib, regorafenib) at low and high doses. Antiangiogenic activity was assessed by CD31⁺ microvessel density (MVD). Transcriptomic remodeling was analyzed by bulk RNA sequencing with gene set variation analysis and principal component analysis. Tumor-infiltrating lymphocytes (TILs) were evaluated for proliferation (Ki67 expression) and interferon-γ (IFN-γ) production. Antitumor efficacy with or without anti–PD-1 was assessed in vivo. Results: All MKIs demonstrated broadly comparable antiangiogenic activity to DC101 (mean CD31+ MVD reduction vs. control: DC101, 27.6%; MKIs: 23.4–42%). Despite this, selective VEGFR2 blockade induced minimal immune perturbation, whereas MKIs induced divergent transcriptomic remodeling across immune, metabolic, stress-response, and proliferation-related pathways. Notably, low-dose cabozantinib and lenvatinib showed reductions in both immune-activating and immune-suppressive gene signatures, suggesting potentially opposing immunologic effects. Functionally, neither DC101 nor MKIs enhanced proliferation or IFN-γ production of tumor-infiltrating T cells. Moreover, MKIs did not improve the antitumor efficacy of anti–PD-1 therapy. Conclusion: Despite similar antiangiogenic effects, MKIs induce broader transcriptomic remodeling without enhancing anti–PD-1 efficacy. These findings suggest that VEGFR-targeting MKIs can induce opposing immune effects beyond VEGF–VEGFR blockade, potentially limiting net enhancement of antitumor immunity.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"13 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atezolizumab plus Bevacizumab Versus Durvalumab plus Tremelimumab in Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Multicenter Retrospective Study","authors":"Yasuto Takeuchi,Shigeo Shimose,Joji Tani,Takanori Ito,Takanori Matsuura,Yuichi Honma,Norikazu Tanabe,Tetsu Tomonari,Nobuhito Taniki,Ryu Sasaki,Takeshi Hatanaka,Satoru Kakizaki,Kyo Sasaki,Naoki Yoshioka,Takafumi Yamamoto,Takehito Naito,Mamiko Takeuchi,Tetsuya Yasunaka,Tomotake Shirono,Takaya Suzuki,Rintaro Kobayashi,Atsushi Naganuma,Sohji Nishina,Hisamitsu Miyaaki,Nobuhiro Nakamoto,Tetsuji Takayama,Taro Takami,Masaru Harada,Yuzo Kodama,Hiroki Kawashima,Hideki Kobara,Takumi Kawaguchi,Motoyuki Otsuka","doi":"10.1159/lic/admag015","DOIUrl":"https://doi.org/10.1159/lic/admag015","url":null,"abstract":"Background: The optimal ICI-based systemic treatment for unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), particularly main portal vein invasion, remains unclear. We compared atezolizumab plus bevacizumab (ATZ/BEV) and durvalumab plus tremelimumab (DUR/TRE) according to PVTT extent. Methods: This multicenter retrospective study included 1,015 patients treated with ATZ/BEV and 186 treated with DUR/TRE. Treatment response, progression-free survival (PFS), overall survival (OS), and safety were compared between groups. Subgroup analyses were performed according to PVTT extent. Results: In the overall cohort, the objective response rate was comparable between the ATZ/BEV and DUR/TRE groups (31.0% vs. 31.7%, P = 0.86), whereas the disease control rate was significantly higher in the ATZ/BEV (78.4% vs. 62.4%, P < 0.01). Median PFS was significantly longer with ATZ/BEV than with DUR/TRE (6.9 vs. 5.3 months, P = 0.049), whereas median OS was comparable between groups (24.9 vs. 31.0 months, P = 0.72). In subgroup analyses stratified by PVTT extent, PFS and OS were generally comparable in patients with Vp1–Vp3 disease. However, among patients with Vp4 disease, median OS was significantly longer with ATZ/BEV than with DUR/TRE (16.6 vs. 6.1 months; HR, 3.60; 95% CI, 1.33–9.74; P < 0.01). The OS difference in Vp4 disease was attenuated and no longer significant in an 8-week landmark analysis. Conclusions: ATZ/BEV was associated with a longer PFS than DUR/TRE in the overall cohort. In patients with Vp4 PVTT, ATZ/BEV may be associated with favorable survival outcomes; however, these findings should be considered hypothesis-generating and require validation.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"54 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Portal vein tumor thrombus in hepatocellular carcinoma: an immune sanctuary driving immune exclusion and therapeutic resistance","authors":"Xingfei Li,Qian Cheng,Jiye Zhu,Zhigao Yuan,Shaowei Mu,Tong Zhou,Jie Gao","doi":"10.1159/lic/admag011","DOIUrl":"https://doi.org/10.1159/lic/admag011","url":null,"abstract":"Background: Portal vein tumor thrombus (PVTT) is the most common form of macrovascular invasion in hepatocellular carcinoma (HCC) and is associated with poor prognosis, rapid intrahepatic dissemination, and limited responsiveness to systemic therapy. Increasing evidence indicates that PVTT is not merely an intravascular extension of the primary tumor, but rather a biologically distinct and highly adaptive immunosuppressive niche that contributes to immune escape and therapeutic resistance. Summary: This review summarizes current genomic, transcriptomic, single-cell, and spatially resolved evidence regarding the immune landscape of PVTT in HCC. We discuss how early clonal divergence, hypoxia-associated metabolic rewiring, and stromal-vascular remodeling cooperatively shape the PVTT microenvironment. PVTT is characterized by enrichment of suppressive myeloid populations, activation of cancer-associated fibroblast programs, extracellular matrix accumulation, endothelial barriers to immune-cell trafficking, and progressive dysfunction or exclusion of effector lymphocytes. Together, these features establish a strongly immune-excluded and immunosuppressive ecosystem, providing a mechanistic basis for the limited efficacy of immune checkpoint blockade in patients with HCC-PVTT. We further highlight the translational implications of this framework for biomarker development, patient stratification, and rational combination strategies targeting suppressive myeloid and stromal programs, vascular barriers, and metabolic-immune crosstalk. Key Messages: PVTT should be regarded as a distinct immunosuppressive niche rather than a passive vascular extension of the primary tumor. Its immune landscape is shaped by coordinated interactions among tumor evolution, metabolic adaptation, stromal remodeling, and immune dysfunction. A better mechanistic understanding of PVTT may support biomarker-guided stratification and the development of more effective precision therapies for HCC with macrovascular invasion.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"143 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}