The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 15, 2023

Adenosine monophosphate-activated protein kinase (AMPK) is a key metabolic sensor that pivotal for the maintenance of cellular energy homeostasis. AMPK contributes to diverse and physiological effects besides its fundamental role in glucose lipid metabolism. Aberrancy signaling one determining factors which lead development chronic diseases such as obesity, inflammation, diabetes, cancer. The activation downstream cascades orchestrate dynamic changes tumor bioenergetics. It well documented possesses suppressor context progression by modulating inflammatory pathways. In addition, plays central potentiating phenotypic functional reprogramming various classes immune cells reside microenvironment (TME). Furthermore, AMPK-mediated responses facilitate recruitment certain types TME, impedes development, progression, metastasis Thus, appears play an important regulation anti-tumor response regulating plasticity cells. effectuates modulation immunity via nutrient TME virtue molecular crosstalk with major checkpoints. Several studies including from our lab emphasize on anticancer several phytochemicals, are potential drug candidates. scope this review encompasses significance cancer metabolism influence drivers within special emphasis use phytochemicals target combat

Language: Английский

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Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside

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

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Circadian regulation of liver function: from molecular mechanisms to disease pathophysiology

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(11), P. 695 - 707

Published: June 8, 2023

Language: Английский

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Expression of tumor antigens within an oncolytic virus enhances the anti-tumor T cell response

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 27, 2024

Abstract Although patients benefit from immune checkpoint inhibition (ICI) therapy in a broad variety of tumors, resistance may arise suppressive tumor microenvironments (TME), which is particularly true hepatocellular carcinoma (HCC). Since oncolytic viruses (OV) can generate highly immune-infiltrated, inflammatory TME, OVs could potentially restore ICI responsiveness via recruitment, priming, and activation anti-tumor T cells. Here we find that on the contrary, an vesicular stomatitis virus, expressing interferon-ß (VSV-IFNß), antagonizes effect anti-PD-L1 partially anti-PD-L1-responsive model HCC. Cytometry by Time Flight shows VSV-IFNß expands dominant anti-viral effector CD8 cells with concomitant relative disappearance cell populations, are target anti-PD-L1. However, range HCC antigens within VSV, combination OV therapeutic be restored. Our data provide cautionary message for use immunogenic as tumor-specific immune-therapeutics showing responses inhibit sub-dominant responses. through encoding virotherapy populations upon blockade effectively work.

Language: Английский

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Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma

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

Published: April 4, 2024

Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays critical role regulating tumor progression and resistance to therapy, HCC, (TME) is characterized by an abundance immunosuppressive cells signals that facilitate evasion metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed modulate system recognize eliminate have become important cornerstone therapy. Immunotherapy has demonstrated ability improve survival provide durable control certain groups HCC patients, while reducing adverse side effects. These findings represent significant step toward improving treatment outcomes. As clinical trials, administration checkpoint inhibitors (ICIs), particularly combination with anti-angiogenic agents tyrosine kinase inhibitors, prolonged subset patients providing alternative for who progress on first-line In this review, we aimed overview its development, summarize trials involving ICIs, either as monotherapies or other disease. Challenges considerations regarding ICIs are also outlined.

Language: Английский

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Cancer-associated fibroblasts in hepatocellular carcinoma: heterogeneity, mechanisms and therapeutic targets

Hepatology International, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Language: Английский

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The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, predominantly associated with chronic hepatitis B virus (HBV) and C (HCV) infections. These infections drive persistent liver inflammation, culminating in cellular dysregulation, fibrosis, cancer. Despite advancements targeted therapies, drug resistance the lack reliable biomarkers for patient stratification still terribly hinder treatment viral HCC. To this end, review delves into intricate mechanisms underlying malignant transformation to HCC, including integration, genomic instability, epigenetic modifications, oxidative stress, gut microbiota dysbiosis, immune escape, abnormal signaling pathways, highlighting their complex interactions synergies. Cutting-edge preclinical clinical HCC management, lifestyle immunotherapies, gene-based approaches, innovative treatments, are further investigated, particular priority given therapeutic potential future applications overcoming current limitations. By synthesizing recent scientific insights, aims deepen understanding pathogenesis context hepatitis, paving way novel targets personalized strategies, ultimately improving outcomes.

Language: Английский

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Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7024 - 7024

Published: June 24, 2022

Circular RNAs (circRNAs), a class of new endogenous non-coding (ncRNAs), are closely related to the carcinogenic process and play critical role in tumor metastasis. CircRNAs can lay foundation for metastasis via promoting angiogenesis, make cells gain ability migration invasion by regulating epithelial-mesenchymal transition (EMT), interact with immune cells, cytokines, chemokines, other non-cellular components microenvironment, damage normal function or escape immunosuppressive network, further promote cell survival Herein, based on characteristics biological functions circRNA, we elaborated effect circRNA circRNA-associated competing RNA (ceRNA) network acting as miRNA/isomiR sponges cancer invasion, interaction microenvironment (TME), then explored potential interactions across different RNAs, finally discussed clinical value application promising biomarker. These results provide theoretical basis metastasis-related circRNAs treatment. In summary, briefly summarize diverse roles ceRNA application, especially miRNA/isomiR, which may complicate regulatory will contribute novel insight into future.

Language: Английский

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LncRNA MEG3 Inhibits Tumor Progression by Modulating Macrophage Phenotypic Polarization via miR-145-5p/DAB2 Axis in Hepatocellular Carcinoma

Journal of Hepatocellular Carcinoma, Journal Year: 2023, Volume and Issue: Volume 10, P. 1019 - 1035

Published: July 1, 2023

Hepatocellular carcinoma (HCC) is the predominant histological type of primary liver cancer, which ranks sixth among most common human tumors. Tumor-associated macrophages (TAMs) are an important component tumor microenvironment (TME) and M2 macrophage polarization substantially contributes to growth metastasis. Long non-coding RNA (lncRNA) MEG3 was reported restrain HCC development. However, whether regulates phenotypic in remains unclear.Bone marrow derived (BMDMs) were treated with LPS/IFNγ IL4/IL13 induce M1 polarization, respectively. M2-polarized BMDMs simultaneously transfected adenovirus vector overexpressing (Adv-MEG3). Subsequently, cultured for 24 h serum-free medium, supernatants harvested as conditioned medium (CM). cell line Huh7 CM h. F4/80+CD68+ F4/80+CD206+ percentages M1-and calculated using flow cytometry. migration, invasion angiogenesis determined via Transwell assay tube formation experiment. Nude mice implanted cells Adv-MEG3-transfected M2-polarizd BMDMs, markers assessed. The binding between miR-145-5p or disabled-2 (DAB2) verified by luciferase reporter assay.MEG3 presented lower expression tissues than normal controls, low correlated poorer prognosis patients. enhanced during LPS/IFNγ-induced but reduced IL4/IL13-induced polarization. overexpression inhibited both mice. Mechanically, bound regulate DAB2 expression. Overexpressing suppressed polarization-induced metastasis upregulating vivo growth.LncRNA curbs development repressing miR-145-5p/DAB2 axis.

Language: Английский

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Ferroptosis targeting natural compounds as a promising approach for developing potent liver cancer agents

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

Published: April 26, 2024

Liver cancer is the second leading cause of cancer-related death worldwide. However, treatment options, including surgical resection, transplantation, and molecular drug therapies, are limited effectiveness. Recent studies have demonstrated that suppressing ferroptosis might be a pivotal signal for liver initiation, thus providing new way to combat cancer. Ferroptosis distinct form controlled cell differs from conventional routes like apoptosis, necrosis, pyroptosis. It results intracellular iron overload, which raises iron-dependent reactive oxygen species. This, in turn, leads accumulation lipid peroxides further result oxidative damage membranes, disrupt normal functioning, ultimately speed up phenomenon. regulation intricately linked cellular physiological processes, encompassing metabolism, equilibrium between oxygen-free radical reactions peroxidation. This review intends summarize natural compounds targeting offer therapeutic ideas Furthermore, it serves as foundation identifying applying chemical medicines chemicals target treat efficiently.

Language: Английский

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