Angiotensin II receptor inhibition ameliorates liver fibrosis and enhances hepatocellular carcinoma infiltration by effector T cells DOI Creative Commons
Li Gu, Yahui Zhu,

Maiya Lee

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(19)

Published: May 1, 2023

Although viral hepatocellular carcinoma (HCC) is declining, nonviral HCC, which often the end stage of nonalcoholic or alcoholic steatohepatitis (NASH, ASH), on an upward trajectory. Immune checkpoint inhibitors (ICIs) that block T cell inhibitory receptor PD-1 were approved for treatment all HCC types. However, only a minority patients show robust and sustained response to blockade, calling improved understanding factors negatively impact rate duration discovery new adjuvant treatments enhance ICI responsiveness. Using mouse model NASH-driven we identified peritumoral fibrosis as potential obstacle cell–mediated tumor regression postulated antifibrotic medications may increase We now angiotensin II inhibitor losartan, commonly prescribed safe antihypertensive drug, reduced liver substantially enhanced anti-PD-1-induced regression. losartan did not potentiate reinvigoration, it infiltration by effector CD8 + cells compared blockade alone. The beneficial effects correlated with blunted TGF-β signaling, collagen deposition, depletion immunosuppressive fibroblasts.

Language: Английский

Precision treatment in advanced hepatocellular carcinoma DOI Creative Commons
Xupeng Yang, Chen Yang, Shu Zhang

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 180 - 197

Published: Feb. 1, 2024

The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, newly developed strategies have not achieved universal success and HCC patients frequently exhibit therapeutic resistance to these therapies. Precision represents a paradigm shift cancer recent years. This approach utilizes unique molecular characteristics individual patient personalize modalities, aiming maximize efficacy while minimizing side effects. Although precision shown multiple types, its application remains infancy. In this review, we discuss key aspects HCC, including biomarkers, classifications, heterogeneity tumor microenvironment. We also propose future directions, ranging from revolutionizing current methodologies personalizing therapy through functional assays, which will accelerate next phase advancements area.

Language: Английский

Citations

139
The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism DOI Open Access

Lingyu Tian,

Daniel J. Smit, Manfred Jücker

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2652 - 2652

Published: Jan. 31, 2023

Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related deaths in world. Metabolic reprogramming considered a new hallmark cancer, but it remains unclearly described HCC. The dysregulation PI3K/AKT/mTOR signaling pathway common HCC and is, therefore, topic further research concern developing novel target for liver cancer therapy. In this review, we illustrate mechanisms by which network accountable regulating cellular metabolism, including glucose lipid amino acid pyrimidine oxidative summarize ongoing clinical trials based on inhibition

Language: Английский

Citations

138
Immune checkpoint inhibitors in hepatocellular carcinoma: emerging challenges in clinical practice DOI
Matthias Pinter, Bernhard Scheiner, David J. Pinato

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2023, Volume and Issue: 8(8), P. 760 - 770

Published: June 16, 2023

Language: Английский

Citations

59
Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives DOI Creative Commons

Ke-Yu Shen,

Ying Zhu,

Sun‐Zhe Xie

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 29, 2024

Abstract Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs been trend this area. Recently, dual blockade durvalumab plus tremelimumab has also emerged an effective for advanced However, majority HCC patients obtain benefits. Understanding immunological rationale exploring novel ways to improve efficacy immunotherapy drawn much attention. review, we summarize latest area, ongoing clinical trials immune-based therapies, well strategies chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, bispecific antibodies.

Language: Английский

Citations

49
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

36
TGF-β1-Induced SOX18 Elevation Promotes Hepatocellular Carcinoma Progression and Metastasis Through Transcriptionally Upregulating PD-L1 and CXCL12 DOI Creative Commons
Jie Chen,

Weibo Feng,

Mengyu Sun

et al.

Gastroenterology, Journal Year: 2024, Volume and Issue: 167(2), P. 264 - 280

Published: Feb. 27, 2024

Hepatocellular carcinoma (HCC) is characterized by an immune-suppressive microenvironment, which contributes to tumor progression, metastasis, and immunotherapy resistance. Identification of HCC-intrinsic factors regulating the immunosuppressive microenvironment urgently needed. Here, we aimed elucidate role SYR-Related High-Mobility Group Box 18 (SOX18) in inducing immunosuppression validate novel combination strategies for SOX18-mediated HCC progression metastasis.

Language: Английский

Citations

30
Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside DOI Creative Commons
Yue Yin,

Weibo Feng,

Jie Chen

et al.

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Language: Английский

Citations

29
YTHDF2 Is a Therapeutic Target for HCC by Suppressing Immune Evasion and Angiogenesis Through ETV5/PD‐L1/VEGFA Axis DOI Creative Commons
Jingyuan Wen, Xue Lin, Wei Yi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 21, 2024

Abstract N6‐methyladenosine (m 6 A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion angiogenesis are characteristic features of its TME. The role YTH RNA binding protein 2 (YTHDF2), as an m A reader, in regulating HCC TME not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 27 acetylation promoter region YTHDF2 enhanced expression HCC, upregulated predicted a worse prognosis. Animal experiments demonstrated Ythdf2 depletion inhibited spontaneous formation, while overexpression promoted xenografted progression. Mechanistically, recognized 5′‐untranslational ETS variant transcription factor 5 (ETV5) mRNA recruited eukaryotic translation initiation 3 subunit B to facilitate translation. Elevated ETV5 induced programmed death ligand‐1 vascular endothelial growth A, thereby promoting angiogenesis. Targeting via small interference RNA‐containing aptamer/liposomes successfully both Together, this findings reveal potential application prognosis targeted treatment.

Language: Английский

Citations

27
Nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma previously treated with sorafenib: 5-year results from CheckMate 040 DOI Creative Commons
Ignacio Melero, Thomas Yau, Yoon‐Koo Kang

et al.

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(6), P. 537 - 548

Published: May 22, 2024

Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort.

Language: Английский

Citations

23
The protein circPETH-147aa regulates metabolic reprogramming in hepatocellular carcinoma cells to remodel immunosuppressive microenvironment DOI Creative Commons
Tian Lan, Fengwei Gao, Yunshi Cai

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Metabolic reprogramming fuels cancer cell metastasis and remodels the immunosuppressive tumor microenvironment (TME). We report here that circPETH, a circular RNA (circRNA) transported via extracellular vesicles (EVs) from tumor-associated macrophages (TAMs) to hepatocellular carcinoma (HCC) cells, facilitates glycolysis in recipient HCC cells. Mechanistically, circPETH-147aa, encoded by circPETH an m6A-driven manner, promotes PKM2-catalyzed ALDOA-S36 phosphorylation MEG pocket. Furthermore, circPETH-147aa impairs anti-HCC immunity increasing HuR-dependent SLC43A2 mRNA stability driving methionine leucine deficiency cytotoxic CD8+ T Importantly, through virtual experimental screening, we find small molecule, Norathyriol, is effective inhibitor targets pocket on surface. Norathyriol reverses circPETH-147aa-facilitated acquisition of metabolic metastatic phenotypes increases anti-PD1 efficacy, enhances T-cell function. Here show promising agent contributes attenuating resistance advanced immune checkpoint blocker (ICB) therapies. Tumor-associated are associated with poor prognosis low responses immunotherapy. Here, authors discover RNA, produced TAMs generates activity CD8 +

Language: Английский

Citations

4